黄芩素通过激活Caspases和Bcl-2家族蛋白诱导卵巢癌HO-8910细胞凋亡
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摘要
目的研究黄芩素对卵巢癌HO-8910细胞凋亡的调控作用及其可能的作用机制。方法选取人卵巢癌细胞系HO-8910细胞,经黄芩素不同浓度及不同时间处理后,分别采用噻唑蓝(MTT)法测定对细胞增殖的影响;采用流式细胞仪检测细胞凋亡和细胞周期;采用Westernblotting法检测Bcl-2家族蛋白表达情况。结果黄芩素对HO-8910细胞有明显的增殖抑制作用,呈浓度-时间依赖性。与对照组比较,黄芩素组细胞凋亡率明显升高(P<0.05、0.01)。黄芩素上调Bax/Bcl-2值,上调cleaved Caspase-3及cleaved Caspase-9的蛋白表达量,呈浓度依赖性。结论黄芩素通过激活Caspase和Bcl-2家族蛋白对卵巢癌HO-8910细胞发挥抗增殖及诱导凋亡活性。
Objective To explore the apoptotic effect of baicalein, a coumarin flavonone, on human ovarian carcinoma HO-8910 cells, as well as the mechanisms. Methods HO-8910 cells were treated with esculetin at a series of concentrations for different times.Expression of apoptosis related Bax/Bcl-2, and Caspases proteins in esculetin treated HO-8910 cells were detected by Western blotting.Cell growth and apoptosis were measured by MTT test and flow cytometry in vitro. Results Cell viability assay showed that esculetin had obvious anti-proliferation effects on HO-8910 cells in a dose-and time-dependent manner. Compared with control group, the group treated with esculetin showed a significant increase in apoptosis rate(P < 0.05, P < 0.01). The results demonstrated that esculetin up-regulated the Bax/Bcl-2 ratio and cleaved Caspase-3, cleaved Caspase-9 expression in a dose-dependent manner. Conclusion In summary, baicalein exerts anti-growth and induced-apoptosis activity against ovarian cancer HO-8910 cells through activating Caspase and Bcl-2 family proteins, therefore presenting as a promising therapeutic agent for the treatment of ovarian cancer.
Objective To explore the apoptotic effect of baicalein, a coumarin flavonone, on human ovarian carcinoma HO-8910 cells, as well as the mechanisms. Methods HO-8910 cells were treated with esculetin at a series of concentrations for different times.Expression of apoptosis related Bax/Bcl-2, and Caspases proteins in esculetin treated HO-8910 cells were detected by Western blotting.Cell growth and apoptosis were measured by MTT test and flow cytometry in vitro. Results Cell viability assay showed that esculetin had obvious anti-proliferation effects on HO-8910 cells in a dose-and time-dependent manner. Compared with control group, the group treated with esculetin showed a significant increase in apoptosis rate(P < 0.05, P < 0.01). The results demonstrated that esculetin up-regulated the Bax/Bcl-2 ratio and cleaved Caspase-3, cleaved Caspase-9 expression in a dose-dependent manner. Conclusion In summary, baicalein exerts anti-growth and induced-apoptosis activity against ovarian cancer HO-8910 cells through activating Caspase and Bcl-2 family proteins, therefore presenting as a promising therapeutic agent for the treatment of ovarian cancer.
引文
[1]Vetter M H,Hays J L.Use of targeted therapeutics in epithelial ovarian cancer:A review of current literature and future directions[J].Clin Ther,2018,40(3):361-371.
[2]Caracciolo G,Palchetti S,Digiacomo L,et al.Human biomolecular corona of liposomal doxorubicin:The overlooked factor in anticancer drug delivery[J].ACSAppl Mater Interfaces,2018,10(27):22951-22962.
[3]Liu X,Wei L,Zhao B,et al.Low expression of KCNN3may affect drug resistance in ovarian cancer[J].Mol Med Rep,2018,18(2):1377-1386.
[4]Vuong Q V,Hirun S,Phillips P A,et al.Fruit-derived phenolic compounds and pancreatic cancer:Perspectives from Australian native fruits[J].J Ethnopharmacol,2014,152(2):227-242.
[5]Suwanamornlert P,Sangchote S,Chinsirikul W,et al.Antifungal activity of plant-derived compounds and their synergism against major postharvest pathogens of longan fruit in vitro[J].Int J Food Microbiol,2018,271(1):8-14.
[6]Zhang J,Chen D,Han D M,et al.Tannic acid mediated induction of apoptosis in human glioma Hs 683 cells[J].Oncol Lett,2018,15(5):6845-6850.
[7]Metere A,Giacomelli L.Absorption,metabolism and protective role of fruits and vegetables polyphenols against gastric cancer[J].Eur Rev Med Pharmacol Sci,2017,21(24):5850-5858.
[8]Su M Q,Zhou Y R,Rao X,et al.Baicalein induces the apoptosis of HCT116 human colon cancer cells via the upregulation of DEPP/Gadd45a and activation of MAPKs[J].Int J Oncol,2018,53(2):750-760.
[9]Yu X,Cao Y,Tang L,et al.Baicalein inhibits breast cancer growth via activating a novel isoform of the long noncoding RNA PAX8-AS1-N[J].J Cell Biochem,2018,119(8):6842-6856.
[10]Su G,Chen H,Sun X.Baicalein suppresses non small cell lung cancer cell proliferation,invasion and Notch signaling pathway[J].Cancer Biomark,2018,22(1):13-18.
[11]Lazzari R,Ronchi S,Gandini S,et al.Stereotactic body radiation therapy for oligometastatic ovarian cancer:Astep toward a drug holiday[J].Int J Radiat Oncol Biol Phys,2018,101(3):650-660.
[12]Aqil F,Jeyabalan J,Agrawal A K,et al.Exosomal delivery of berry anthocyanidins for the management of ovarian cancer[J].Food Funct,2017,8(11):4100-4107.
[13]Tao W,Luo X,Cui B,et al.Practice of traditional Chinese medicine for psycho-behavioral intervention improves quality of life in cancer patients:A systematic review and meta-analysis[J].Oncotarget,2015,6(37):39725-39739.
[14]Wang Z,Qi F,Cui Y,et al.An update on Chinese herbal medicines as adjuvant treatment of anticancer therapeutics[J].Biosci Trends,2018,12(3):220-239.
[15]Liu Y,Tong L,Luo Y,et al.Resveratrol inhibits the proliferation and induces the apoptosis in ovarian cancer cells via inhibiting glycolysis and targeting AMPK/mTOR signaling pathway[J].J Cell Biochem,2018,119(7):6162-6172.
[16]张黎媛.白藜芦醇及其代谢产物与类似物抗癌症转移作用机制研究进展[J].中草药,2017,48(20):4346-4352.
[17]姜程曦,吴亮,吴洁,等.姜黄素类似物抑制ERK/JNK以及NF-κB信号通路发挥抗炎活性研究[J].中草药,2016,47(16):2871-2876.
[18]余展鹏,宋方茗,蔡琰,等.黄芩素对鼻咽癌CNE2细胞增殖和凋亡的影响[J].中草药,2018,49(4):879-884.
[19]Qin G,Li P,Xue Z.Triptolide induces protective autophagy and apoptosis in human cervical cancer cells by downregulating Akt/mTOR activation[J].Oncol Lett,2018,16(3):3929-3934.
[20]Li J,Li H,Li Q,et al.Repaglinide inhibits cyclosporine A-induced renal tubular toxicity by affecting apoptosis and Bax and Bcl-2 expression[J].Turk J Med Sci,2018,48(4):880-885.
[21]Chen C,Liu T S,Zhao S C,et al.XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma[J].Exp Ther Med,2018,15(5):4587-4593.
[22]Zhang K,Ge Z,Fu L,et al.Qilin pills alleviate oligoasthenospermia by inhibiting Bax-caspase-9apoptosis pathway in the testes of model rats[J].Oncotarget,2018,9(31):21770-21782.
[23]Iwai N,Yasui K,Tomie A,et al.Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma[J].Int J Oncol,2018,53(1):237-245.
[2]Caracciolo G,Palchetti S,Digiacomo L,et al.Human biomolecular corona of liposomal doxorubicin:The overlooked factor in anticancer drug delivery[J].ACSAppl Mater Interfaces,2018,10(27):22951-22962.
[3]Liu X,Wei L,Zhao B,et al.Low expression of KCNN3may affect drug resistance in ovarian cancer[J].Mol Med Rep,2018,18(2):1377-1386.
[4]Vuong Q V,Hirun S,Phillips P A,et al.Fruit-derived phenolic compounds and pancreatic cancer:Perspectives from Australian native fruits[J].J Ethnopharmacol,2014,152(2):227-242.
[5]Suwanamornlert P,Sangchote S,Chinsirikul W,et al.Antifungal activity of plant-derived compounds and their synergism against major postharvest pathogens of longan fruit in vitro[J].Int J Food Microbiol,2018,271(1):8-14.
[6]Zhang J,Chen D,Han D M,et al.Tannic acid mediated induction of apoptosis in human glioma Hs 683 cells[J].Oncol Lett,2018,15(5):6845-6850.
[7]Metere A,Giacomelli L.Absorption,metabolism and protective role of fruits and vegetables polyphenols against gastric cancer[J].Eur Rev Med Pharmacol Sci,2017,21(24):5850-5858.
[8]Su M Q,Zhou Y R,Rao X,et al.Baicalein induces the apoptosis of HCT116 human colon cancer cells via the upregulation of DEPP/Gadd45a and activation of MAPKs[J].Int J Oncol,2018,53(2):750-760.
[9]Yu X,Cao Y,Tang L,et al.Baicalein inhibits breast cancer growth via activating a novel isoform of the long noncoding RNA PAX8-AS1-N[J].J Cell Biochem,2018,119(8):6842-6856.
[10]Su G,Chen H,Sun X.Baicalein suppresses non small cell lung cancer cell proliferation,invasion and Notch signaling pathway[J].Cancer Biomark,2018,22(1):13-18.
[11]Lazzari R,Ronchi S,Gandini S,et al.Stereotactic body radiation therapy for oligometastatic ovarian cancer:Astep toward a drug holiday[J].Int J Radiat Oncol Biol Phys,2018,101(3):650-660.
[12]Aqil F,Jeyabalan J,Agrawal A K,et al.Exosomal delivery of berry anthocyanidins for the management of ovarian cancer[J].Food Funct,2017,8(11):4100-4107.
[13]Tao W,Luo X,Cui B,et al.Practice of traditional Chinese medicine for psycho-behavioral intervention improves quality of life in cancer patients:A systematic review and meta-analysis[J].Oncotarget,2015,6(37):39725-39739.
[14]Wang Z,Qi F,Cui Y,et al.An update on Chinese herbal medicines as adjuvant treatment of anticancer therapeutics[J].Biosci Trends,2018,12(3):220-239.
[15]Liu Y,Tong L,Luo Y,et al.Resveratrol inhibits the proliferation and induces the apoptosis in ovarian cancer cells via inhibiting glycolysis and targeting AMPK/mTOR signaling pathway[J].J Cell Biochem,2018,119(7):6162-6172.
[16]张黎媛.白藜芦醇及其代谢产物与类似物抗癌症转移作用机制研究进展[J].中草药,2017,48(20):4346-4352.
[17]姜程曦,吴亮,吴洁,等.姜黄素类似物抑制ERK/JNK以及NF-κB信号通路发挥抗炎活性研究[J].中草药,2016,47(16):2871-2876.
[18]余展鹏,宋方茗,蔡琰,等.黄芩素对鼻咽癌CNE2细胞增殖和凋亡的影响[J].中草药,2018,49(4):879-884.
[19]Qin G,Li P,Xue Z.Triptolide induces protective autophagy and apoptosis in human cervical cancer cells by downregulating Akt/mTOR activation[J].Oncol Lett,2018,16(3):3929-3934.
[20]Li J,Li H,Li Q,et al.Repaglinide inhibits cyclosporine A-induced renal tubular toxicity by affecting apoptosis and Bax and Bcl-2 expression[J].Turk J Med Sci,2018,48(4):880-885.
[21]Chen C,Liu T S,Zhao S C,et al.XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma[J].Exp Ther Med,2018,15(5):4587-4593.
[22]Zhang K,Ge Z,Fu L,et al.Qilin pills alleviate oligoasthenospermia by inhibiting Bax-caspase-9apoptosis pathway in the testes of model rats[J].Oncotarget,2018,9(31):21770-21782.
[23]Iwai N,Yasui K,Tomie A,et al.Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma[J].Int J Oncol,2018,53(1):237-245.