灵芝酸A对前列腺癌LNCaP细胞的生长抑制作用及机制
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摘要
本研究利用alamarBlue~?测定细胞活力法、流式细胞术(annxin V-FITC)/PI双染色测定细胞凋亡法和高效液相色谱(high performance liquid chromatography,HPLC)测定5α-还原酶活性法评价灵芝酸A对前列腺癌的体外抗肿瘤活性,并进一步利用流式细胞术2’,7’-二氯荧光素二乙酸酯(2’,7’-dichlorofluorescindiacetate,H2DCFDA)染色测定ROS释放量法、实时荧光定量PCR(quantitative real-time PCR,qPCR)和蛋白质免疫印迹(western blot,WB)检测雄激素受体(androgen receptor,AR)基因和凋亡相关基因表达的方法,探讨其作用机理。研究结果表明灵芝酸A可通过抑制5α-还原酶活性,抑制睾酮诱导的前列腺癌LNCaP细胞增殖,诱发细胞早期凋亡来发挥抗肿瘤活性;进一步研究表明,灵芝酸A降低前列腺癌细胞中AR的表达,并通过引发细胞线粒体功能障碍释放过量活性氧(reactive oxygen species,ROS)诱发细胞凋亡,而qPCR和WB的数据进一步表明细胞线粒体功能障碍与抑癌基因caspase-3、bad和aifm1的高表达密切相关。
AlamarBlue~? method, flow cytometry(Annxin V-FITC)/PI double staining method and HPLC method were used to evaluate anti-tumor activity of ganoderic acid A(GA-A) against prostate cancer in vitro. Flow cytometry 2',7'-dichlorofluorescindiacetate(H2 DCFDA) staining, quantitative real-time PCR(qPCR) and western blot(WB) were used to explore the mechanism of anti-tumor action. The results indicated that ganoderic acid A(GA-A) could exert its anti-tumor effect by reducing 5-reductase activity, inhibiting the proliferation and inducing early apoptosis of prostate cancer LNCaP cells. The results further showed that GA-A could reduce the expression of androgen receptor and induce apoptosis by triggering mitochondrial dysfunction to release excessive reactive oxygen species(ROS). Realtime PCR and WB data indicated that cell mitochondrial dysfunction was closely related to the high expression of tumor suppressor genes caspase-3,bad and aifm1.
AlamarBlue~? method, flow cytometry(Annxin V-FITC)/PI double staining method and HPLC method were used to evaluate anti-tumor activity of ganoderic acid A(GA-A) against prostate cancer in vitro. Flow cytometry 2',7'-dichlorofluorescindiacetate(H2 DCFDA) staining, quantitative real-time PCR(qPCR) and western blot(WB) were used to explore the mechanism of anti-tumor action. The results indicated that ganoderic acid A(GA-A) could exert its anti-tumor effect by reducing 5-reductase activity, inhibiting the proliferation and inducing early apoptosis of prostate cancer LNCaP cells. The results further showed that GA-A could reduce the expression of androgen receptor and induce apoptosis by triggering mitochondrial dysfunction to release excessive reactive oxygen species(ROS). Realtime PCR and WB data indicated that cell mitochondrial dysfunction was closely related to the high expression of tumor suppressor genes caspase-3,bad and aifm1.
引文
Bray F,Ferlay J,Soerjomataram I,Siegel RL,Torre LA,Jemal A,2018.Global cancer statistics 2018:Globocan estimates of incidence and mortality worldwide for 36 cancers in185 countries.CA A Cancer Journal for Clinicians,68(6):394-424
Cao Y,Wu SH,Dai YC,2012.Species clarification of the prize medicinal Ganoderma mushroom“Lingzhi”.Fungal Diversity,56:49-62
Center MM,Jemal A,Lortet-Tieulent J,Ward E,Ferlay J,Brawley O,Bray F,2012.International variation in prostate cancer incidence and mortality rates.European Urology Focus,61(6):1079-1092
Chen W,Zheng R,Baade PD,Zhang S,Zeng H,Bray F,Jemal A,Yu XQ,He J,2016.Cancer statistics in China,2015.CA ACancer Journal for Clinicians,66(2):115-132
Dai YC,Cao Y,Zhou LW,Wu SH,2013.Notes on the nomenclature of the most widely cultivated Ganoderma species in China.Mycosystema,32(6):947-952(in Chinese)
Fizazi K,Tran N,Fein L,Matsubara N,RodriguezAntolin A,Alekseev BY,?zgüro?lu M,Ye D,Feyerabend S,Protheroe A,2017.Abiraterone plus prednisone in metastatic,castration-sensitive prostate cancer.The New England Journal of Medicine,377(4):352-360
Fujita R,Liu J,Shimizu K,Konishi F,Noda K,Kumamoto S,Ueda C,Tajiri H,Kaneko S,Suimi Y,Kondo R,2005.Anti-androgenic activities of Ganoderma lucidum.Journal of Ethnopharmacology,102(1):107-112
Gelmann EP,2002.Molecular biology of the androgen receptor.Journal of Clinical Oncology:Official Journal of the American Society of Clinical Oncology,20(13):3001
Ghavami S,Kerkhoff C,Los M,Hashemi M,Sorg C,Karamitehrani F,2004.Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines:the role of ROSand the effect of metal ions.Journal of Leukocyte Biology,76(1):169-175
Gomella LG,2017.Prostate cancer statistics:anything you want them to be.The Canadian Journal of Urology,24(1):8603-8604
Hattori T,Ookawa N,Fujita R,Fukuchi K,2000.Heterodimerization of Bcl-2 and Bcl-X(L)with Bax and Bad in colorectal cancer.Acta Radiologica,39(4):495-500
Hsieh TC,Wu JM,2002.Mechanism of action of herbal supplement PC-SPES:elucidation of effects of individual herbs of PC-SPES on proliferation and prostate specific gene expression in androgen-dependent LNCaP cells.International Journal of Oncology,20(3):583-588
Huang P,2004.ROS stress in cancer cells and therapeutic implications.Drug Resistance Updates:Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy,7(2):97-110
James ND,Bono JSD,Spears MR,Clarke NW,Mason MD,Dearnaley DP,Ritchie AWS,Amos CL,Gilson C,Jones RJ,2017.Abiraterone for prostate cancer not previously treated with hormone therapy.The New England Journal of Medicine,377(4):338
James ND,Sydes MR,Clarke NW,Mason MD,Dearnaley DP,Spears MR,Ritchie AW,Parker CC,Russell JM,Attard G,2016.Addition of docetaxel,zoledronic acid,or both to first-line long-term hormone therapy in prostate cancer(STAMPEDE):survival results from an adaptive,multiarm,multistage,platform randomised controlled trial.The Lancet,387(10024):1163-1177
Jiang J,Slivova V,Valachovicova T,Harvey K,Sliva D,2004.Ganoderma lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3.International Journal of Oncology,24(5):1093-1099
Kasahara Y,Iwai K,Yachie A,Ohta K,Konno A,Seki H,Miyawaki T,Taniguchi N,1997.Involvement of reactive oxygen intermediates in spontaneous and cd95(fas/apo-1)-mediated apoptosis of neutrophils.Blood,89(5):1748-1753
Li CH,Jia W,Yang HR,Sun TP,Zhuang HN,Chen J,Xi LP,Wang WH,2016.Immunological,anti-oxidant and antitumor activity of artificially cultivated Xylaria nigripes fruit body extracts.Acta Edulis Fungi,23(2):59-64(in Chinese)
Liu J,Shimizu K,Kondo R,2010.The effects of ganoderma alcohols isolated from Ganoderma lucidum on the androgen receptor binding and the growth of LNCaPcells.Fitoterapia,81(8):1067-1072
Liu J,Tamura S,Kurashiki K,Shimizu K,Noda K,Konishi F,Kumamoto S,Kondo R,2010.Anti-androgen effects of extracts and compounds from Ganoderma lucidum.Chemistry and Biodiversity,6(2):231-243
Liu QM,2003.Benign prostatic hyperplasia:dialectical unity of cell proliferation and apoptosis.Journal of Jiujiang University(Natural Science Edition),18(2):60-62(in Chinese)
Miyamoto H,Altuwaijri S,Chang C,2004.Androgen receptor in prostate cancer progression.Endocrine Reviews,25(2):276-308.
Pan ES,Li YG,2017.Effect of ganoderma acid A on apoptosis of human prostate cancer cell line DU-145.Guangdong Medical Journal,38(1):87-90(in Chinese)
Pierce GB,Parchment RE,Lewellyn AL,2010.Hydrogen peroxide as a mediator of programmed cell death in the blastocyst.Research in Biological Diversity,46(3):181-186
Porter AG,J?nicke RU,1999.Emerging roles of caspase-3 in apoptosis.Cell Death and Differentiation,6(2):99-104
Russell DW,Wilson JD,1994.Steroid 5 alpha-reductase:two genes/two enzymes.Annual Review of Biochemistry,63(1):25-61
Schlegel J,Peters I,Orrenius S,Miller DK,Thornberry NA,Yamin TT,Nicholson DW,1996.CPP32/apopain is a key interleukin 1 converting enzyme-like protease involved in Fas-mediated apoptosis.The Journal of Biological Chemistry,271(4):1841-1844
Shi L,Ren A,Mu D,Zhao M,2010.Current progress in the study on biosynthesis and regulation of ganoderic acids.Applied Microbiology and Biotechnology,88(6):1243-1251
Simon HU,Hajyehia A,Levischaffer F,2000.Role of reactive oxygen species(ROS)in apoptosis induction.Apoptosis,5(5):415-418
Sliva D,Labarrere C,Slivova V,Sedlak M,Lloyd F,Ho N,2002.Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells.Biochemical and Biophysical Research Communications,298(4):603-612
Sliva D,Sedlak M,Slivova V,Valachovicova T,Lloyd F,Ho N,2003.Biologic activity of spores and dried powder from Ganoderma lucidum for the inhibition of highly invasive human breast and prostate cancer cells.Journal of Alternative and Complementary Medicine,9(4):491
Song C,Guo SC,2013.Molecular cloning and characterization of a hemolysin gene from medicinal fungus Polyporus umbellatus.Mycosystema,32(4):690-697(in Chinese)
Sweeney CJ,Chen YH,Carducci M,Liu G,Jarrard DF,Eisenberger M,Wong YN,Hahn N,Kohli M,Cooney MM,2015.Chemohormonal therapy in metastatic hormone-sensitive prostate cancer.The New England Journal of Medicine,373(8):737
Wang T,Xie ZP,Huang ZS,Li H,Wei AY,Di JM,Xiao HJ,Zhang ZG,Cai LH,Tao X,2015.Total triterpenoids from Ganoderma lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.Journal of Huazhong University of Science and Technology(Medical Sciences),35(5):736-741
Wang WH,Jia W,Yang HR,Sun TP,Zhuang HN,Chen J,Xi LP,Li CH,Zhang JS,2017.Bioactivities of mycelia from a Xylaria sp.strain.Mycosystema,36(6):730-742(in Chinese)
Wang WH,Xu B,Zhang HN,Yang Y,Zhuang HN,Tang CH,Xu J,Jia W,Zhang JS,2017.A toxicological study on ethanol extract from fruiting bodies of Ganoderma lingzhi.Mycosystema,36(12):1642-1650(in Chinese)
Wang WH,Zhu LN,Zhang HN,Yang Y,Zhuang HN,Tang CH,Liu YF,Xu B,Jia W,Zhang JS,2018.Screening of mushroom ethanol extract inhibiting prostate cancer and cancer-inhibitory mechanism of Ganoderma lingzhi extract.Mycosystema,37(6):782-793(in Chinese)
Wang X,Zelenski NG,Yang J,Sakai J,Brown MS,Goldstein JL,1996.Cleavage of sterol regulatory element binding proteins(SREBPs)by CPP32 during apoptosis.The Embo Journal,15(5):1012-1020
Wei YF,Gu XJ,Zhu QY,2016.New progress in the treatment of castration resistant prostate cancer.Chinese Journal of Andrology,22(5):455-461(in Chinese)
Weng D,Lu Y,Wei Y,Liu Y,Shen P,2007.The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury in mice.Toxicology,232(1):15-23
Yang J,Liu X,Bhalla K,Kim CN,Ibrado AM,Cai J,Peng TI,Jones DP,Wang X,1997.Prevention of apoptosis by Bcl-2:release of cytochrome c from mitochondria blocked.Science,275(5303):1129-1132
Zhang H,Zhang JS,Feng N,Wang WH,Tang CH,Yang Y,Jia W,Tang QJ,Pan YJ,2013.Effect of ganodermanontriol on the LNCaP cell and 5α-reductase.Natural Product Research and Development,25(10):1416-1419(in Chinese)
戴玉成,曹云,周丽伟,吴声华,2013.中国灵芝学名之管见.菌物学报,32(6):947-952
李传华,贾薇,杨海芮,孙太萍,庄海宁,陈杰,奚利萍,汪雯翰,2016.人工栽培黑柄炭角菌子实体的生物活性.食用菌学报,23(2):59-64
刘庆猛,2003.良性前列腺增生:细胞增殖与细胞凋亡的辨证统一.九江学院学报(自然科学版),18(2):60-62
潘恩山,李煜罡,2017.灵芝酸A对人前列腺癌细胞DU-145细胞凋亡的影响.广东医学,38(1):87-90
宋超,郭顺星,2013.药用真菌猪苓溶血素基因克隆和序列分析.菌物学报,32(4):690-697
汪雯翰,贾薇,杨海芮,孙太萍,庄海宁,陈杰,奚莉萍,李传华,张劲松,2017.一种炭角菌菌丝体生物活性的研究.菌物学报,36(6):730-742
汪雯翰,徐宾,张赫男,杨焱,庄海宁,唐传红,徐錦,贾薇,张劲松,2017.灵芝子实体醇提取物的毒理研究.菌物学报,36(12):1642-1650
汪雯翰,朱丽娜,张赫男,杨焱,庄海宁,唐传红,刘艳芳,徐宾,贾薇,张劲松,2018.抑制前列腺癌的食药用菌醇提物的筛选及灵芝醇提物对癌细胞的抑制机理.菌物学报,37(6):782-793
魏云飞,顾晓箭,朱清毅,2016.去势抵抗性前列腺癌的治疗新进展.中华男科学杂志,22(5):455-461
章慧,张劲松,冯娜,汪雯翰,唐传红,杨焱,贾薇,唐庆九,潘迎捷,2013.灵芝酮三醇对人前列腺癌细胞LNCaP生长的影响及其对5α-还原酶的抑制作用.天然产物研究与开发,25(10):1416-1419
Cao Y,Wu SH,Dai YC,2012.Species clarification of the prize medicinal Ganoderma mushroom“Lingzhi”.Fungal Diversity,56:49-62
Center MM,Jemal A,Lortet-Tieulent J,Ward E,Ferlay J,Brawley O,Bray F,2012.International variation in prostate cancer incidence and mortality rates.European Urology Focus,61(6):1079-1092
Chen W,Zheng R,Baade PD,Zhang S,Zeng H,Bray F,Jemal A,Yu XQ,He J,2016.Cancer statistics in China,2015.CA ACancer Journal for Clinicians,66(2):115-132
Dai YC,Cao Y,Zhou LW,Wu SH,2013.Notes on the nomenclature of the most widely cultivated Ganoderma species in China.Mycosystema,32(6):947-952(in Chinese)
Fizazi K,Tran N,Fein L,Matsubara N,RodriguezAntolin A,Alekseev BY,?zgüro?lu M,Ye D,Feyerabend S,Protheroe A,2017.Abiraterone plus prednisone in metastatic,castration-sensitive prostate cancer.The New England Journal of Medicine,377(4):352-360
Fujita R,Liu J,Shimizu K,Konishi F,Noda K,Kumamoto S,Ueda C,Tajiri H,Kaneko S,Suimi Y,Kondo R,2005.Anti-androgenic activities of Ganoderma lucidum.Journal of Ethnopharmacology,102(1):107-112
Gelmann EP,2002.Molecular biology of the androgen receptor.Journal of Clinical Oncology:Official Journal of the American Society of Clinical Oncology,20(13):3001
Ghavami S,Kerkhoff C,Los M,Hashemi M,Sorg C,Karamitehrani F,2004.Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines:the role of ROSand the effect of metal ions.Journal of Leukocyte Biology,76(1):169-175
Gomella LG,2017.Prostate cancer statistics:anything you want them to be.The Canadian Journal of Urology,24(1):8603-8604
Hattori T,Ookawa N,Fujita R,Fukuchi K,2000.Heterodimerization of Bcl-2 and Bcl-X(L)with Bax and Bad in colorectal cancer.Acta Radiologica,39(4):495-500
Hsieh TC,Wu JM,2002.Mechanism of action of herbal supplement PC-SPES:elucidation of effects of individual herbs of PC-SPES on proliferation and prostate specific gene expression in androgen-dependent LNCaP cells.International Journal of Oncology,20(3):583-588
Huang P,2004.ROS stress in cancer cells and therapeutic implications.Drug Resistance Updates:Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy,7(2):97-110
James ND,Bono JSD,Spears MR,Clarke NW,Mason MD,Dearnaley DP,Ritchie AWS,Amos CL,Gilson C,Jones RJ,2017.Abiraterone for prostate cancer not previously treated with hormone therapy.The New England Journal of Medicine,377(4):338
James ND,Sydes MR,Clarke NW,Mason MD,Dearnaley DP,Spears MR,Ritchie AW,Parker CC,Russell JM,Attard G,2016.Addition of docetaxel,zoledronic acid,or both to first-line long-term hormone therapy in prostate cancer(STAMPEDE):survival results from an adaptive,multiarm,multistage,platform randomised controlled trial.The Lancet,387(10024):1163-1177
Jiang J,Slivova V,Valachovicova T,Harvey K,Sliva D,2004.Ganoderma lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3.International Journal of Oncology,24(5):1093-1099
Kasahara Y,Iwai K,Yachie A,Ohta K,Konno A,Seki H,Miyawaki T,Taniguchi N,1997.Involvement of reactive oxygen intermediates in spontaneous and cd95(fas/apo-1)-mediated apoptosis of neutrophils.Blood,89(5):1748-1753
Li CH,Jia W,Yang HR,Sun TP,Zhuang HN,Chen J,Xi LP,Wang WH,2016.Immunological,anti-oxidant and antitumor activity of artificially cultivated Xylaria nigripes fruit body extracts.Acta Edulis Fungi,23(2):59-64(in Chinese)
Liu J,Shimizu K,Kondo R,2010.The effects of ganoderma alcohols isolated from Ganoderma lucidum on the androgen receptor binding and the growth of LNCaPcells.Fitoterapia,81(8):1067-1072
Liu J,Tamura S,Kurashiki K,Shimizu K,Noda K,Konishi F,Kumamoto S,Kondo R,2010.Anti-androgen effects of extracts and compounds from Ganoderma lucidum.Chemistry and Biodiversity,6(2):231-243
Liu QM,2003.Benign prostatic hyperplasia:dialectical unity of cell proliferation and apoptosis.Journal of Jiujiang University(Natural Science Edition),18(2):60-62(in Chinese)
Miyamoto H,Altuwaijri S,Chang C,2004.Androgen receptor in prostate cancer progression.Endocrine Reviews,25(2):276-308.
Pan ES,Li YG,2017.Effect of ganoderma acid A on apoptosis of human prostate cancer cell line DU-145.Guangdong Medical Journal,38(1):87-90(in Chinese)
Pierce GB,Parchment RE,Lewellyn AL,2010.Hydrogen peroxide as a mediator of programmed cell death in the blastocyst.Research in Biological Diversity,46(3):181-186
Porter AG,J?nicke RU,1999.Emerging roles of caspase-3 in apoptosis.Cell Death and Differentiation,6(2):99-104
Russell DW,Wilson JD,1994.Steroid 5 alpha-reductase:two genes/two enzymes.Annual Review of Biochemistry,63(1):25-61
Schlegel J,Peters I,Orrenius S,Miller DK,Thornberry NA,Yamin TT,Nicholson DW,1996.CPP32/apopain is a key interleukin 1 converting enzyme-like protease involved in Fas-mediated apoptosis.The Journal of Biological Chemistry,271(4):1841-1844
Shi L,Ren A,Mu D,Zhao M,2010.Current progress in the study on biosynthesis and regulation of ganoderic acids.Applied Microbiology and Biotechnology,88(6):1243-1251
Simon HU,Hajyehia A,Levischaffer F,2000.Role of reactive oxygen species(ROS)in apoptosis induction.Apoptosis,5(5):415-418
Sliva D,Labarrere C,Slivova V,Sedlak M,Lloyd F,Ho N,2002.Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells.Biochemical and Biophysical Research Communications,298(4):603-612
Sliva D,Sedlak M,Slivova V,Valachovicova T,Lloyd F,Ho N,2003.Biologic activity of spores and dried powder from Ganoderma lucidum for the inhibition of highly invasive human breast and prostate cancer cells.Journal of Alternative and Complementary Medicine,9(4):491
Song C,Guo SC,2013.Molecular cloning and characterization of a hemolysin gene from medicinal fungus Polyporus umbellatus.Mycosystema,32(4):690-697(in Chinese)
Sweeney CJ,Chen YH,Carducci M,Liu G,Jarrard DF,Eisenberger M,Wong YN,Hahn N,Kohli M,Cooney MM,2015.Chemohormonal therapy in metastatic hormone-sensitive prostate cancer.The New England Journal of Medicine,373(8):737
Wang T,Xie ZP,Huang ZS,Li H,Wei AY,Di JM,Xiao HJ,Zhang ZG,Cai LH,Tao X,2015.Total triterpenoids from Ganoderma lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.Journal of Huazhong University of Science and Technology(Medical Sciences),35(5):736-741
Wang WH,Jia W,Yang HR,Sun TP,Zhuang HN,Chen J,Xi LP,Li CH,Zhang JS,2017.Bioactivities of mycelia from a Xylaria sp.strain.Mycosystema,36(6):730-742(in Chinese)
Wang WH,Xu B,Zhang HN,Yang Y,Zhuang HN,Tang CH,Xu J,Jia W,Zhang JS,2017.A toxicological study on ethanol extract from fruiting bodies of Ganoderma lingzhi.Mycosystema,36(12):1642-1650(in Chinese)
Wang WH,Zhu LN,Zhang HN,Yang Y,Zhuang HN,Tang CH,Liu YF,Xu B,Jia W,Zhang JS,2018.Screening of mushroom ethanol extract inhibiting prostate cancer and cancer-inhibitory mechanism of Ganoderma lingzhi extract.Mycosystema,37(6):782-793(in Chinese)
Wang X,Zelenski NG,Yang J,Sakai J,Brown MS,Goldstein JL,1996.Cleavage of sterol regulatory element binding proteins(SREBPs)by CPP32 during apoptosis.The Embo Journal,15(5):1012-1020
Wei YF,Gu XJ,Zhu QY,2016.New progress in the treatment of castration resistant prostate cancer.Chinese Journal of Andrology,22(5):455-461(in Chinese)
Weng D,Lu Y,Wei Y,Liu Y,Shen P,2007.The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury in mice.Toxicology,232(1):15-23
Yang J,Liu X,Bhalla K,Kim CN,Ibrado AM,Cai J,Peng TI,Jones DP,Wang X,1997.Prevention of apoptosis by Bcl-2:release of cytochrome c from mitochondria blocked.Science,275(5303):1129-1132
Zhang H,Zhang JS,Feng N,Wang WH,Tang CH,Yang Y,Jia W,Tang QJ,Pan YJ,2013.Effect of ganodermanontriol on the LNCaP cell and 5α-reductase.Natural Product Research and Development,25(10):1416-1419(in Chinese)
戴玉成,曹云,周丽伟,吴声华,2013.中国灵芝学名之管见.菌物学报,32(6):947-952
李传华,贾薇,杨海芮,孙太萍,庄海宁,陈杰,奚利萍,汪雯翰,2016.人工栽培黑柄炭角菌子实体的生物活性.食用菌学报,23(2):59-64
刘庆猛,2003.良性前列腺增生:细胞增殖与细胞凋亡的辨证统一.九江学院学报(自然科学版),18(2):60-62
潘恩山,李煜罡,2017.灵芝酸A对人前列腺癌细胞DU-145细胞凋亡的影响.广东医学,38(1):87-90
宋超,郭顺星,2013.药用真菌猪苓溶血素基因克隆和序列分析.菌物学报,32(4):690-697
汪雯翰,贾薇,杨海芮,孙太萍,庄海宁,陈杰,奚莉萍,李传华,张劲松,2017.一种炭角菌菌丝体生物活性的研究.菌物学报,36(6):730-742
汪雯翰,徐宾,张赫男,杨焱,庄海宁,唐传红,徐錦,贾薇,张劲松,2017.灵芝子实体醇提取物的毒理研究.菌物学报,36(12):1642-1650
汪雯翰,朱丽娜,张赫男,杨焱,庄海宁,唐传红,刘艳芳,徐宾,贾薇,张劲松,2018.抑制前列腺癌的食药用菌醇提物的筛选及灵芝醇提物对癌细胞的抑制机理.菌物学报,37(6):782-793
魏云飞,顾晓箭,朱清毅,2016.去势抵抗性前列腺癌的治疗新进展.中华男科学杂志,22(5):455-461
章慧,张劲松,冯娜,汪雯翰,唐传红,杨焱,贾薇,唐庆九,潘迎捷,2013.灵芝酮三醇对人前列腺癌细胞LNCaP生长的影响及其对5α-还原酶的抑制作用.天然产物研究与开发,25(10):1416-1419