吡柔比星联合羟喜树碱灌注化疗对晚期膀胱癌细胞恶性生物学行为的影响
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摘要
目的探讨吡柔比星联合羟喜树碱灌注化疗对晚期膀胱癌细胞恶性生物学行为的影响。方法收集77例晚期膀胱癌患者的临床资料,按膀胱灌注化疗方案分为吡柔比星组40例与联合治疗组37例。吡柔比星组患者采用吡柔比星灌注化疗,联合治疗组采用吡柔比星联合羟喜树碱灌注化疗。比较两组患者灌注化疗后膀胱癌细胞增殖、侵袭、凋亡基因的相对表达量。结果联合治疗组增殖基因ABCE1、KPNA2、MRPS5、YAP的mRNA相对表达量均低于吡柔比星组,DKK2、LASS2的mRNA相对表达量均高于吡柔比星组(均P <0. 05);联合治疗组侵袭基因ILK、NF-κBp65、HMGB1的mRNA相对表达量均低于吡柔比星组,PPARγ的mRNA相对表达量高于吡柔比星组(均P <0. 05);联合治疗组凋亡基因Livin、Survivin、BAG-1的mRNA相对表达量均低于吡柔比星组,Bad、Caspase-3的mRNA相对表达量均高于吡柔比星组(均P <0. 05)。结论相比于单用吡柔比星膀胱灌注化疗,采用吡柔比星联合羟喜树碱膀胱灌注化疗治疗晚期膀胱癌更能有效抑制癌细胞的增殖、侵袭活力,并促进癌细胞凋亡。
Objective To investigate the effect of infusion chemotherapy using hydroxycamptothecine combined with pirarubicin on malignant biological behaviors in advanced bladder cancer cells. Methods The clinical data of 77 patients with advanced bladder cancer were collected,and the patients were divided into pirarubicin group( n = 40) and combined treatment group( n = 37) according to their bladder infusion chemotherapy regimens. The pirarubicin group received infusion chemotherapy of pirarubicin,while the combined treatment group received infusion chemotherapy of hydroxycamptothecine combined with pirarubicin. The relative expression of proliferation,invasion and apoptosis genes was compared between the two groups after infusion chemotherapy. Results The combined treatment group had lower relative expression of proliferation genes ABCE1,KPNA2,MRPS5 and YAP mRNAs,and higher relative expression of DKK2 and LASS2 mRNAs than the pirarubicin group( all P < 0. 05); the combined treatment group exhibited lower relative expression of invasion genes ILK,NF-κBp65 and HMGB1 mRNAs,and higher relative expression of PPARγ mRNA than the pirarubicin group( all P < 0. 05); the combined treatment group reported lower relative expression of apoptosis genes Livin,Survivin and BAG-1 mRNAs,and higher relative expression of Bad and Caspase-3 mRNAs than the pirarubicin group( all P < 0. 05). Conclusion As compared to infusion chemotherapy of pirarubicin alone,infusion chemotherapy of hydroxycamptothecin combined with pirarubicin can inhibit the proliferation and invasion activity of cancer cells more effectively and promote the apoptosis of cancer cells in the treatment of advanced bladder cancer.
Objective To investigate the effect of infusion chemotherapy using hydroxycamptothecine combined with pirarubicin on malignant biological behaviors in advanced bladder cancer cells. Methods The clinical data of 77 patients with advanced bladder cancer were collected,and the patients were divided into pirarubicin group( n = 40) and combined treatment group( n = 37) according to their bladder infusion chemotherapy regimens. The pirarubicin group received infusion chemotherapy of pirarubicin,while the combined treatment group received infusion chemotherapy of hydroxycamptothecine combined with pirarubicin. The relative expression of proliferation,invasion and apoptosis genes was compared between the two groups after infusion chemotherapy. Results The combined treatment group had lower relative expression of proliferation genes ABCE1,KPNA2,MRPS5 and YAP mRNAs,and higher relative expression of DKK2 and LASS2 mRNAs than the pirarubicin group( all P < 0. 05); the combined treatment group exhibited lower relative expression of invasion genes ILK,NF-κBp65 and HMGB1 mRNAs,and higher relative expression of PPARγ mRNA than the pirarubicin group( all P < 0. 05); the combined treatment group reported lower relative expression of apoptosis genes Livin,Survivin and BAG-1 mRNAs,and higher relative expression of Bad and Caspase-3 mRNAs than the pirarubicin group( all P < 0. 05). Conclusion As compared to infusion chemotherapy of pirarubicin alone,infusion chemotherapy of hydroxycamptothecin combined with pirarubicin can inhibit the proliferation and invasion activity of cancer cells more effectively and promote the apoptosis of cancer cells in the treatment of advanced bladder cancer.
引文
[1] Lewis GD,Haque W,Verma V,et al. The role of adjuvant radiation therapy in locally advanced bladder cancer[J].Bladder Cancer,2018,4(2):205-213.
[2] Morales-Barrera R,Gonzlez M,Surez C,et al. Detection of circulating tumor DNA for advanced bladder cancer:where are we going?[J]. Transl Androl Urol,2018,7(Suppl 1):S101-S103.
[3] Ba MC,Cui SZ,Wang B,et al. Bladder intracavitary hyperthermic perfusion chemotherapy for the prevention of recurrence of non-muscle invasive bladder cancer after transurethral resection[J]. Oncol Rep,2017,37(5):2 761-2 770.
[4]中国医师协会泌尿外科医师分会肿瘤专业委员会,中国医师协会泌尿外科医师分会上尿路尿路上皮癌(CUDAUTUC)协作组.上尿路尿路上皮癌诊断与治疗中国专家共识[J].中华泌尿外科杂志,2018,39(7):485-488.
[5] Wang LH,Shang L,Shan DY,et al. Long-term floating controlreleased intravesical preparation of 5-fluorouracil for the local treatment of bladder cancer[J]. Drug Dev Ind Pharm,2017,43(8):1 343-1 350.
[6] Wei YJ,Li CH,Zhang Y,et al. Hydroxycamptothecin mediates antiproliferative effects through apoptosis and autophagy in A549 cells[J]. Oncol Lett,2018,15(5):6 322-6 328.
[7] Wen Y,Zhang W,Gong NQ,et al. Carrier-free,self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo[J]. Nanoscale,2017,9(38):14 347-14 356.
[8] Tian Y,Tian X,Han X,et al. ABCE1 plays an essential role in lung cancer progression and metastasis[J]. Tumor Biol,2016,37(6):8 375-8 382.
[9] Zheng DW,Dai Y,Wang S,et al. MicroRNA-299-3p promotes the sensibility of lung cancer to doxorubicin through directly targeting ABCE1[J]. Int J Clin Exp Pathol,2015,8(9):10 072-10 081.
[10] Huang L,Zhou Y,Cao XP,et al. KPNA2 promotes migration and invasion in epithelial ovarian cancer cells by inducing epithelial-mesenchymal transition via Akt/GSK-3beta/Snail activation[J]. J Cancer,2018,9(1):157-165.
[11] Tsai MM,Huang HW,Wang CS,et al. MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer[J]. Oncotarget,2016,7(26):39 511-39 526.
[12] Lee J,Seol MY,Jeong S,et al. A metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma[J].Medicine(Baltimore),2015,94(2):e380.
[13] Oku Y,Nishiya N,Sugiyama S,et al. Sensitisation of cancer cells to MLN8237,an Aurora-A inhibitor,by YAP/TAZ inactivation[J]. Anticancer Res,2018,38(6):3 471-3 476.
[14] Zheng L,Xiang C,Li X,et al. STARD13-correlated ceRNA network-directed inhibition on YAP/TAZ activity suppresses stemness of breast cancer via co-regulating Hippo and RhoGTPase/F-actin signaling[J]. J Hematol Oncol,2018,11(1):72.
[15] Wang H,Duan XL,Qi XL,et al. Concurrent hypermethylation of SFRP2 and DKK2 activates the Wnt/β-catenin pathway and is associated with poor prognosis in patients with gastric cancer[J]. Mol Cells,2017,40(1):45-53.
[16] Luan T,Zou R,Huang L,et al. Hsa-miR-3658 promotes cell proliferation,migration and invasion by effecting LASS2 in bladder cancer[J]. Clin Lab,2018,64(4):515-525.
[17] Tsoumas D,Nikou S,Giannopoulou E,et al. ILK expression in colorectal cancer is associated with EMT,cancer stem cell markers and chemoresistance[J]. Cancer Genomics Proteomics,2018,15(2):127-141.
[18] Sndergaard JN,Poghosyan S,Hontelez S,et al. DC-SCRIPT regulates IL-10 production in human dendritic cells by modulating NF-κBp65 activation[J]. J Immunol,2015,195(4):1 498-1 505.
[19] Li SY,Wei YL. Association of HMGB1,BRCA1 and P62expression in ovarian cancer and chemotherapy sensitivity[J].Oncol Lett,2018,15(6):9 572-9 576.
[20] Wu L,Yang LL. The function and mechanism of HMGB1 in lung cancer and its potential therapeutic implications[J].Oncol Lett,2018,15(5):6 799-6 805.
[21] Xiong LG,Liang BW,Bai MS,et al. Impact of interaction between PPAR alpha and PPAR gamma on breast cancer risk in the Chinese Han population[J]. Clin Breast Cancer,2017,17(5):336-340.
[22]徐海波,熊异平,余恒勇.膀胱癌组织中MMP-2、MMP-9、Survivin、Livin和VEGF表达的临床意义分析[J].标记免疫分析与临床,2017,24(1):51-54.
[23] Liu S,Li X,Li Q,et al. Silencing Livin improved the sensitivity of colon cancer cells to 5-fluorouracil by regulating crosstalk between apoptosis and autophagy[J]. Oncol Lett,2018,15(5):7 707-7 715.
[24] Li D,He S. MAGE3 and Survivin activated dendritic cell immunotherapy for the treatment of non-small cell lung cancer[J]. Oncol Lett,2018,15(6):8 777-8 783.
[25] Yosefzon Y,Soteriou D,Feldman A,et al. Caspase-3 regulates YAP-dependent cell proliferation and organ size[J]. Mol Cell,2018,70(4):573-587.
[26] Sauerbrei W,Haeussler T. Comment on,BAG-1 as a biomarker in early breast cancer prognosis:a systematic review with metaanalyses'[J]. Br J Cancer,2018,118(8):1 152-1 153.
[2] Morales-Barrera R,Gonzlez M,Surez C,et al. Detection of circulating tumor DNA for advanced bladder cancer:where are we going?[J]. Transl Androl Urol,2018,7(Suppl 1):S101-S103.
[3] Ba MC,Cui SZ,Wang B,et al. Bladder intracavitary hyperthermic perfusion chemotherapy for the prevention of recurrence of non-muscle invasive bladder cancer after transurethral resection[J]. Oncol Rep,2017,37(5):2 761-2 770.
[4]中国医师协会泌尿外科医师分会肿瘤专业委员会,中国医师协会泌尿外科医师分会上尿路尿路上皮癌(CUDAUTUC)协作组.上尿路尿路上皮癌诊断与治疗中国专家共识[J].中华泌尿外科杂志,2018,39(7):485-488.
[5] Wang LH,Shang L,Shan DY,et al. Long-term floating controlreleased intravesical preparation of 5-fluorouracil for the local treatment of bladder cancer[J]. Drug Dev Ind Pharm,2017,43(8):1 343-1 350.
[6] Wei YJ,Li CH,Zhang Y,et al. Hydroxycamptothecin mediates antiproliferative effects through apoptosis and autophagy in A549 cells[J]. Oncol Lett,2018,15(5):6 322-6 328.
[7] Wen Y,Zhang W,Gong NQ,et al. Carrier-free,self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo[J]. Nanoscale,2017,9(38):14 347-14 356.
[8] Tian Y,Tian X,Han X,et al. ABCE1 plays an essential role in lung cancer progression and metastasis[J]. Tumor Biol,2016,37(6):8 375-8 382.
[9] Zheng DW,Dai Y,Wang S,et al. MicroRNA-299-3p promotes the sensibility of lung cancer to doxorubicin through directly targeting ABCE1[J]. Int J Clin Exp Pathol,2015,8(9):10 072-10 081.
[10] Huang L,Zhou Y,Cao XP,et al. KPNA2 promotes migration and invasion in epithelial ovarian cancer cells by inducing epithelial-mesenchymal transition via Akt/GSK-3beta/Snail activation[J]. J Cancer,2018,9(1):157-165.
[11] Tsai MM,Huang HW,Wang CS,et al. MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer[J]. Oncotarget,2016,7(26):39 511-39 526.
[12] Lee J,Seol MY,Jeong S,et al. A metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma[J].Medicine(Baltimore),2015,94(2):e380.
[13] Oku Y,Nishiya N,Sugiyama S,et al. Sensitisation of cancer cells to MLN8237,an Aurora-A inhibitor,by YAP/TAZ inactivation[J]. Anticancer Res,2018,38(6):3 471-3 476.
[14] Zheng L,Xiang C,Li X,et al. STARD13-correlated ceRNA network-directed inhibition on YAP/TAZ activity suppresses stemness of breast cancer via co-regulating Hippo and RhoGTPase/F-actin signaling[J]. J Hematol Oncol,2018,11(1):72.
[15] Wang H,Duan XL,Qi XL,et al. Concurrent hypermethylation of SFRP2 and DKK2 activates the Wnt/β-catenin pathway and is associated with poor prognosis in patients with gastric cancer[J]. Mol Cells,2017,40(1):45-53.
[16] Luan T,Zou R,Huang L,et al. Hsa-miR-3658 promotes cell proliferation,migration and invasion by effecting LASS2 in bladder cancer[J]. Clin Lab,2018,64(4):515-525.
[17] Tsoumas D,Nikou S,Giannopoulou E,et al. ILK expression in colorectal cancer is associated with EMT,cancer stem cell markers and chemoresistance[J]. Cancer Genomics Proteomics,2018,15(2):127-141.
[18] Sndergaard JN,Poghosyan S,Hontelez S,et al. DC-SCRIPT regulates IL-10 production in human dendritic cells by modulating NF-κBp65 activation[J]. J Immunol,2015,195(4):1 498-1 505.
[19] Li SY,Wei YL. Association of HMGB1,BRCA1 and P62expression in ovarian cancer and chemotherapy sensitivity[J].Oncol Lett,2018,15(6):9 572-9 576.
[20] Wu L,Yang LL. The function and mechanism of HMGB1 in lung cancer and its potential therapeutic implications[J].Oncol Lett,2018,15(5):6 799-6 805.
[21] Xiong LG,Liang BW,Bai MS,et al. Impact of interaction between PPAR alpha and PPAR gamma on breast cancer risk in the Chinese Han population[J]. Clin Breast Cancer,2017,17(5):336-340.
[22]徐海波,熊异平,余恒勇.膀胱癌组织中MMP-2、MMP-9、Survivin、Livin和VEGF表达的临床意义分析[J].标记免疫分析与临床,2017,24(1):51-54.
[23] Liu S,Li X,Li Q,et al. Silencing Livin improved the sensitivity of colon cancer cells to 5-fluorouracil by regulating crosstalk between apoptosis and autophagy[J]. Oncol Lett,2018,15(5):7 707-7 715.
[24] Li D,He S. MAGE3 and Survivin activated dendritic cell immunotherapy for the treatment of non-small cell lung cancer[J]. Oncol Lett,2018,15(6):8 777-8 783.
[25] Yosefzon Y,Soteriou D,Feldman A,et al. Caspase-3 regulates YAP-dependent cell proliferation and organ size[J]. Mol Cell,2018,70(4):573-587.
[26] Sauerbrei W,Haeussler T. Comment on,BAG-1 as a biomarker in early breast cancer prognosis:a systematic review with metaanalyses'[J]. Br J Cancer,2018,118(8):1 152-1 153.