宫颈癌组织中PKCα、PKCε、PKCδ表达及与化疗药物敏感性的机制研究
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摘要
目的:探讨宫颈癌组织中PKCα、PKCε、PKCδ表达及其与化疗药物敏感性的关系。方法:选择本院收治的确诊宫颈癌患者38例,三维彩色多普勒超声检测血管形成指数(VI)、血流指数(FI)、血管血流指数(VFI),取化疗前后病灶组织各100mg左右,采用RT-PCR检测组织中PKCα、PKCε、PKCδmRNA表达水平,Western blot检测组织中PKCα、PKCε、PKCδ蛋白的表达,Spearman相关分析PKCα、PKCε、PKCδmRNA表达水平与化药敏感性的关系,Logisitic回归分析影响化疗敏感性的相关因素。结果:化疗后PKCα、PKCεmRNA和蛋白表达水平均显著降低(P<0.05),PKCδmRNA和蛋白的表达均显著升高(P<0.05);化疗后有效组PKCα、PKCεmRNA和蛋白表达水平较化疗前均显著降低(P<0.05),PKCδmRNA和蛋白的表达较化疗前均显著升高(P<0.05);Spearman分析化疗前宫颈癌组织中PKCα与PKCε的mRNA表达水平与VI、FI和化疗后残余肿瘤体积百分比呈显著正相关,PKCδ与VI、FI和化疗后残余肿瘤体积百分比呈显著负相关,而与VFI和化疗前肿瘤的体积大小无明显相关性;Logisitic回归分析显示PKCα、PKCε、PKCδmRNA、VI、FI为化疗敏感性的独立危险因素,淋巴结转移、肿瘤体积与化疗敏感性无关。结论:PKCα、PKCε在宫颈癌组织中高表达,PKCδ在宫颈癌组织中低表达,三者均与化疗敏感性具有密切关系。
Objective:To investigate the expressions of PKCα ,PKCε and PKCδ in cervical cancer and their relationships with chemosensitivity.Methods:38 cases of patients with cervical cancer diagnosed in our hospital from November 2015 to November 2016 were selected,the vascularization index(VI),flow index(FI)and vascular flow index(VFI)were measured by three-dimensional color Doppler ultrasound,the expression levels of PKCα ,PKCε and PKCδ mRNAs were detected by RTPCR before and after chemotherapy,Western blot was used to detect the expression of PKCα ,PKCε and PKCδ proteins in tissues,Spearman correlation analysis was performed to investigate the relationships between PKCα ,PKCε and PKCδ mRNAswith chemosensitivity,Logisitic regression analysis was used to analyze the related factors affecting the sensitivity of chemotherapy.Results:After chemotherapy,the expression levels of PKCα and PKCε mRNAs and proteins were significantly decreased(P<0.05),the expressions of PKCδ mRNA and protein were significantly increased(P<0.05);the expression levels of PKCα and PKCε mRNAs and proteins in the effective group after chemotherapy were significantly lower than those before chemotherapy(P<0.05),the expressions of PKCδ mRNA and protein were significantly higher than those before chemotherapy(P<0.05);Spearman analysis showed that the expression levels of PKCα and PKCε mRNAs in cervical cancer tissues before chemotherapy were positively correlated with VI,FI and the percentage of residual tumor volume after chemotherapy,PKCδ was negatively correlated with VI,FI and residual tumor volume percentage after chemotherapy,and was not significantly correlated with VFI and tumor size before chemotherapy;Logistic regression analysis showed that PKCα ,PKCε ,PKCδ mRNAs,VI and FI were independent risk factors for chemosensitivity,lymph node metastasis and tumor volume were independent of chemosensitivity.Conclusion:PKCα and PKCε are highly expressed in cervical cancer tissues,and PKCδ is low expressed in cervical cancer tissues,they are closely related to chemosensitivity.
Objective:To investigate the expressions of PKCα ,PKCε and PKCδ in cervical cancer and their relationships with chemosensitivity.Methods:38 cases of patients with cervical cancer diagnosed in our hospital from November 2015 to November 2016 were selected,the vascularization index(VI),flow index(FI)and vascular flow index(VFI)were measured by three-dimensional color Doppler ultrasound,the expression levels of PKCα ,PKCε and PKCδ mRNAs were detected by RTPCR before and after chemotherapy,Western blot was used to detect the expression of PKCα ,PKCε and PKCδ proteins in tissues,Spearman correlation analysis was performed to investigate the relationships between PKCα ,PKCε and PKCδ mRNAswith chemosensitivity,Logisitic regression analysis was used to analyze the related factors affecting the sensitivity of chemotherapy.Results:After chemotherapy,the expression levels of PKCα and PKCε mRNAs and proteins were significantly decreased(P<0.05),the expressions of PKCδ mRNA and protein were significantly increased(P<0.05);the expression levels of PKCα and PKCε mRNAs and proteins in the effective group after chemotherapy were significantly lower than those before chemotherapy(P<0.05),the expressions of PKCδ mRNA and protein were significantly higher than those before chemotherapy(P<0.05);Spearman analysis showed that the expression levels of PKCα and PKCε mRNAs in cervical cancer tissues before chemotherapy were positively correlated with VI,FI and the percentage of residual tumor volume after chemotherapy,PKCδ was negatively correlated with VI,FI and residual tumor volume percentage after chemotherapy,and was not significantly correlated with VFI and tumor size before chemotherapy;Logistic regression analysis showed that PKCα ,PKCε ,PKCδ mRNAs,VI and FI were independent risk factors for chemosensitivity,lymph node metastasis and tumor volume were independent of chemosensitivity.Conclusion:PKCα and PKCε are highly expressed in cervical cancer tissues,and PKCδ is low expressed in cervical cancer tissues,they are closely related to chemosensitivity.
引文
1乔友林,赵宇倩.宫颈癌的流行病学现状和预防[J].中华妇幼临床医学杂志(电子版),2015,11(2):1-6.
2周晖,卢淮武,彭永排,等.《2015年NCCN宫颈癌临床实践指南》解读[J].中国实用妇科与产科杂志,2015,30(3):185-191.
3朱方培,任青玲.宫颈癌及癌前病变早期筛查的新进展[J].现代肿瘤医学,2016,24(1):149-152.
4范桂莲,唐建武,卢红明,等.结肠腺癌中蛋白激酶C亚型的表达及意义[J].新乡医学院学报,2017,34(03):180-183.
5林仲秋,王丽娟,刘龙阳.国际妇产科联盟2012宫颈癌诊治指南解读[J].中国实用妇科与产科杂志,2013,9(5):323-325.
6刘洁瑾,荣良群,魏秀娥,等.蛋白激酶C在细胞凋亡中的研究进展[J].徐州医学院学报,2016,36(4):272-276.
7 Zheng J,Kong C,Yang X,et al.Protein kinase C-α(PKCα)modulates cell apoptosis by stimulating nuclear translocation of NF-kappa-B p65in urothelial cell carcinoma of the bladder.[J].Bmc Cancer,2017,17(1):432-444.
8 Hsu YH,Yao J,Chan LC,et al.Definition of PKC-α,CDK6,and MET as therapeutic targets in triple-negative breast cancer[J].Cancer Research,2015,74(17):4822-4835.
9吴虹,高红变,梁钢,等.小分子干扰RNA干扰蛋白激酶Cα相互作用蛋白1基因对结肠腺癌HT-29细胞增殖凋亡及侵袭的影响[J].中国药物与临床,2016,16(4):467-469.
10 Kim CW,Asai D,Kang JH,et al.Reversal of efflux of an anticancer drug in human drug-resistant breast cancer cells by inhibition of protein kinase Cα(PKCα)activity[J].Tumour Biol,2016,37(2):1901-1908.
11 Liu X,Wang L,Shen Y,et al.Disruption of precise regulation ofαPKC expression and cellular localization is associated with cervical cancer progression[J].Archives of Gynecology&Obstetrics,2013,288(2):401.
12唐广义,韩涛,殷东风,等.益气健脾抗癌法对结肠癌组织PKC及亚型PKCδ、PKCε蛋白表达的影响[J].中国肿瘤生物治疗杂志,2016,23(3):366-370.
13 Li N,Zhang W.Protein kinase Cβinhibits autophagy and sensitizes cervical cancer Hela cells to cisplatin:[J].Bioscience Reports,2017,37(2):BSR20160445.
14益气健脾抗癌法对大肠癌组织VEGF、PKCα、PKCβ蛋白表达影响实验研究[J].辽宁中医药大学学报,2016(5):52-55.
15 Chunmei LI,Zhang Q,Gao T.Effect of PKCε-siRNAon Proliferating and Invading Ability in Human Cervical Cancer ME180Cellline[J].Journal of Practical Obstetrics&Gynecology,2015.
16 Wang X,Tan C,Wang G,et al.Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδin prostatic cancer cells[J].International Journal of Oncology,2017,51(5):1601-1610.
17 Jin C,Ling T,Ma J,et al.Dying tumor cells stimulate proliferation of living tumor cells via caspase-dependent protein kinase Cδactivation in pancreatic ductal adenocarcinoma[J].Molecular Oncology,2015,9(1):105-114.
18整合素-β1、PKC与胶质瘤细胞骨架结构改变及侵袭性的实验研究[J].现代肿瘤医学,2017,25(10):1543-1548.
2周晖,卢淮武,彭永排,等.《2015年NCCN宫颈癌临床实践指南》解读[J].中国实用妇科与产科杂志,2015,30(3):185-191.
3朱方培,任青玲.宫颈癌及癌前病变早期筛查的新进展[J].现代肿瘤医学,2016,24(1):149-152.
4范桂莲,唐建武,卢红明,等.结肠腺癌中蛋白激酶C亚型的表达及意义[J].新乡医学院学报,2017,34(03):180-183.
5林仲秋,王丽娟,刘龙阳.国际妇产科联盟2012宫颈癌诊治指南解读[J].中国实用妇科与产科杂志,2013,9(5):323-325.
6刘洁瑾,荣良群,魏秀娥,等.蛋白激酶C在细胞凋亡中的研究进展[J].徐州医学院学报,2016,36(4):272-276.
7 Zheng J,Kong C,Yang X,et al.Protein kinase C-α(PKCα)modulates cell apoptosis by stimulating nuclear translocation of NF-kappa-B p65in urothelial cell carcinoma of the bladder.[J].Bmc Cancer,2017,17(1):432-444.
8 Hsu YH,Yao J,Chan LC,et al.Definition of PKC-α,CDK6,and MET as therapeutic targets in triple-negative breast cancer[J].Cancer Research,2015,74(17):4822-4835.
9吴虹,高红变,梁钢,等.小分子干扰RNA干扰蛋白激酶Cα相互作用蛋白1基因对结肠腺癌HT-29细胞增殖凋亡及侵袭的影响[J].中国药物与临床,2016,16(4):467-469.
10 Kim CW,Asai D,Kang JH,et al.Reversal of efflux of an anticancer drug in human drug-resistant breast cancer cells by inhibition of protein kinase Cα(PKCα)activity[J].Tumour Biol,2016,37(2):1901-1908.
11 Liu X,Wang L,Shen Y,et al.Disruption of precise regulation ofαPKC expression and cellular localization is associated with cervical cancer progression[J].Archives of Gynecology&Obstetrics,2013,288(2):401.
12唐广义,韩涛,殷东风,等.益气健脾抗癌法对结肠癌组织PKC及亚型PKCδ、PKCε蛋白表达的影响[J].中国肿瘤生物治疗杂志,2016,23(3):366-370.
13 Li N,Zhang W.Protein kinase Cβinhibits autophagy and sensitizes cervical cancer Hela cells to cisplatin:[J].Bioscience Reports,2017,37(2):BSR20160445.
14益气健脾抗癌法对大肠癌组织VEGF、PKCα、PKCβ蛋白表达影响实验研究[J].辽宁中医药大学学报,2016(5):52-55.
15 Chunmei LI,Zhang Q,Gao T.Effect of PKCε-siRNAon Proliferating and Invading Ability in Human Cervical Cancer ME180Cellline[J].Journal of Practical Obstetrics&Gynecology,2015.
16 Wang X,Tan C,Wang G,et al.Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδin prostatic cancer cells[J].International Journal of Oncology,2017,51(5):1601-1610.
17 Jin C,Ling T,Ma J,et al.Dying tumor cells stimulate proliferation of living tumor cells via caspase-dependent protein kinase Cδactivation in pancreatic ductal adenocarcinoma[J].Molecular Oncology,2015,9(1):105-114.
18整合素-β1、PKC与胶质瘤细胞骨架结构改变及侵袭性的实验研究[J].现代肿瘤医学,2017,25(10):1543-1548.