Bcl-xL、Bax和Bcl-2蛋白在大肠癌伴血吸虫病中的表达及其意义
|
摘要
目的检测Bcl-x L、Bax和Bcl-2蛋白在大肠癌伴血吸虫病中的表达,探讨血吸虫感染与大肠癌之间的可能发病机制。方法 76例大肠癌患者分为两组,大肠癌伴血吸虫病组40例及单纯大肠癌组36例。用免疫组化SP法检测Bcl-x L、Bax和Bcl-2蛋白在两组患者中的表达水平。肿瘤HE切片在显微镜下观察细胞形态并进行凋亡率统计。结果在大肠癌伴血吸虫病组及单纯大肠癌两组中,Bcl-x L蛋白的表达强度均为中等,阳性率分别为50.0%,66.7%(P>0.05);在大肠癌伴血吸虫病组中,Bax蛋白的表达强度为中度,阳性率为25.0%,而在单纯大肠癌组中的表达强度为中到强阳性,阳性率为77.8%(P<0.001);Bcl-2蛋白在大肠癌伴血吸虫病组中的表达强度为弱到中度,阳性率为55.0%,而在单纯大肠癌组中的表达强度较弱,阳性率为22.2%(P<0.05)。大肠癌伴血吸虫病组及单纯大肠癌两组的细胞凋亡率分别为15.0%、42.0%(P<0.001)。结论慢性日本血吸虫病与大肠癌之间可能存在一定的关系;在慢性血吸虫病引起的肠粘膜的恶变过程中,Bcl-2和Bax的异常表达,引起凋亡的失调,从而导致肿瘤的发生、发展。
Objective To investigate the relationship between chronic schistosomiasis japonica and colorectal carcinomathrough detecting the expression pattern of Bcl-x L, Bax and Bcl-2 in colorectal carcinoma with schistosomiasis.Methods We divided the colorectal cancer patients in two different groups, one associated with Schistosoma and the otherwithout Schistosoma. The expression of Bcl-x L, Bax and Bcl-2 was detected in 40 cases of colorectal cancer with Schistosoma and 36 colorectal cancer without Schistosoma by S-P immunohistochemical technique, in addition the apoptotic activity ofthese tumor cells were analyzed by HE. Results The immunostaining intensity of Bcl-x L protein in colorectal cancer with Schistosoma and colorectal cancer without Schistosoma were moderate, the positive percentage of Bcl-x L expression incolorectal cancer with Schistosoma group was 50.0%, and it was 66.7% in control group(P>0.05);In colorectal cancer with Schistosoma, the immunostaining intensity of Bax protein was moderate, the positive percentage was 25.0%, and it wassignificantly lower than the control group(77.8%)(P<0.001). The immunostaining intensity of Bcl-2 protein in two groups wereweak, the positive percentage of Bcl-2 expression in colorectal cancer with Schistosoma was 55.0%, and it was significantlyhigher than the control group(22.2%)(P<0.05). Apoptotic activity was more evident in colorectal cancer without Schistosoma group(42.0%) than that of the other group(15.0%)(P<0.001). Conclusion There might be a high correlation between chronicschistosomiasis japonica and colorectal carcinoma. These observations suggest that the genotoxic agents may play a role incolorectal cancer with Schistosoma pathogenesis through the dysregulation of apoptosis by alteration the expression pattern ofBcl-2 and Bax protein differently from colorectal cancer without Schistosoma.
Objective To investigate the relationship between chronic schistosomiasis japonica and colorectal carcinomathrough detecting the expression pattern of Bcl-x L, Bax and Bcl-2 in colorectal carcinoma with schistosomiasis.Methods We divided the colorectal cancer patients in two different groups, one associated with Schistosoma and the otherwithout Schistosoma. The expression of Bcl-x L, Bax and Bcl-2 was detected in 40 cases of colorectal cancer with Schistosoma and 36 colorectal cancer without Schistosoma by S-P immunohistochemical technique, in addition the apoptotic activity ofthese tumor cells were analyzed by HE. Results The immunostaining intensity of Bcl-x L protein in colorectal cancer with Schistosoma and colorectal cancer without Schistosoma were moderate, the positive percentage of Bcl-x L expression incolorectal cancer with Schistosoma group was 50.0%, and it was 66.7% in control group(P>0.05);In colorectal cancer with Schistosoma, the immunostaining intensity of Bax protein was moderate, the positive percentage was 25.0%, and it wassignificantly lower than the control group(77.8%)(P<0.001). The immunostaining intensity of Bcl-2 protein in two groups wereweak, the positive percentage of Bcl-2 expression in colorectal cancer with Schistosoma was 55.0%, and it was significantlyhigher than the control group(22.2%)(P<0.05). Apoptotic activity was more evident in colorectal cancer without Schistosoma group(42.0%) than that of the other group(15.0%)(P<0.001). Conclusion There might be a high correlation between chronicschistosomiasis japonica and colorectal carcinoma. These observations suggest that the genotoxic agents may play a role incolorectal cancer with Schistosoma pathogenesis through the dysregulation of apoptosis by alteration the expression pattern ofBcl-2 and Bax protein differently from colorectal cancer without Schistosoma.
引文
[1]BOTELHO M C,FIGUEIREDO J,ALVES H.Bladder cancer and urinary Schistosomiasis in Angola[J].J Nephrol Res,2015,1(1):22-24.
[2]YI Z,HONG-GANG J,ZHI-HENG C,et al.Short-term efficacy of laparoscopic treatment for colorectal cancer in patients with schistosomiasis japonica[J].Gastroenterol Res Pract,2016,2016:8357025.
[3]LI W C.Sigmoid colonic carcinoma associated with deposited ova of Schistosoma japonicum:A case report[J].World Journal of Gastroenterology,2006,12(37):6077.
[4]H SALIM O E,HAMID H K,MEKKI S O,et al.Colorectal carcinoma associated with schistosomiasis:a possible causal relationship[J].World J Surg Oncol,2010,8:68.
[5]QIU D C,HUBBARD A E,ZHONG B,et al.A matched,case-control study of the association between Schistosoma japonicum and liver and colon cancers,in rural China[J].Ann Trop Med Parasitol,2005,99(1):47-52.
[6]MAHDAVI S,KHODARAHMI P,ROODBARI N.Effects of cadmium on Bcl-2/Bax expression ratio in rat cortex brain and hippocampus[J].Human&Experimental Toxicology,2017,1(1):81-83.
[7]MUCHMORE S W,SATTLER M,LIANG H,et al.X-ray and NMR structure of human Bcl-x L,an inhibitor of programmed cell death[J].Nature,1996,381(6580):335-341.
[8]YOKOYAMA T,KOHN E,BRILL E,et al.Apoptosis is augmented in high-grade serous ovarian cancer by the combined inhibition of Bcl-2/Bcl-x L and PARP[J].International Journal of Oncology,2017,3(15):455-457.
[9]WIWANITKIT V.Re:Prognostic significance of Bcl-x L gene expression in human colorectal cancer[J].Acta Histochem,2012,114(2):182;author reply 183.
[10]YANG J,SUN M,ZHANG A,et al.Adenovirus-mediated si RNA targeting Bcl-x L inhibits proliferation,reduces invasion and enhances radiosensitivity of human colorectal cancer cells[J].World J Surg Oncol,2011,9:117.
[11]BOLENZ C,BECKER A,TROJAN L,et al.Optimizing chemotherapy for transitional cell carcinoma by application of Bcl-2and bcl-x L antisense oligodeoxynucleotides[J].Urol Oncol,2007,25(6):476-482.
[12]陈寅波,刘卓,钱俊,等.DNA错配修复基因h MLH1与h MSH2在结直肠癌合并慢性血吸虫肠病与散发型结直肠癌中表达的差异研究[J].中华胃肠外科杂志,2016,19(1):75-79.
[13]ZHANG R,TAKAHASHI S,ORITA S,et al.p53 gene mutations in rectal cancer associated with schistosomiasis japonica in Chinese patients[J].Cancer Lett,1998,131(2):215-221.
[14]ZALATA K R,NASIF W A,MING S C,et al.p53,Bcl-2 and C-Myc expressions in colorectal carcinoma associated with schistosomiasis in Egypt[J].Cell Oncol,2005,27(4):245-253.
[15]杨道华,邱承敏,孙玮玮,等.应用组织芯片检测慢性血吸虫病合并大肠癌多基因蛋白的表达[J].中国血吸虫病防治杂志,2014,26(4):405-409.
[16]IMAI J,ICHIKAWA H,MIZUKAMI H,et al.Colonic high-grade tubular adenomas associated with Schistosoma japonicum[J].Tokai J Exp Clin Med,2016,41(1):22-23.
[17]白瑞璞,潘卫庆.日本血吸虫感染小鼠肝脏枯否细胞差异表达Micro RNA及基因的分析[J].中国热带医学,2017,17(4):344-349.
[18]FENG H,LU A G,ZHAO X W,et al.Comparison of nonschistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer[J].World J Gastroenterol,2015,21(23):7225-7232.
[19]张利娟,徐志敏,钱颖骏,等.2015年全国血吸虫病疫情通报[J].中国血吸虫病防治杂志,2016,28(6):611-617.
[20]黎文华,王鹏.干细胞治疗人体寄生虫病研究进展[J].中国血吸虫病防治杂志,2016,28(6):740-744.
[2]YI Z,HONG-GANG J,ZHI-HENG C,et al.Short-term efficacy of laparoscopic treatment for colorectal cancer in patients with schistosomiasis japonica[J].Gastroenterol Res Pract,2016,2016:8357025.
[3]LI W C.Sigmoid colonic carcinoma associated with deposited ova of Schistosoma japonicum:A case report[J].World Journal of Gastroenterology,2006,12(37):6077.
[4]H SALIM O E,HAMID H K,MEKKI S O,et al.Colorectal carcinoma associated with schistosomiasis:a possible causal relationship[J].World J Surg Oncol,2010,8:68.
[5]QIU D C,HUBBARD A E,ZHONG B,et al.A matched,case-control study of the association between Schistosoma japonicum and liver and colon cancers,in rural China[J].Ann Trop Med Parasitol,2005,99(1):47-52.
[6]MAHDAVI S,KHODARAHMI P,ROODBARI N.Effects of cadmium on Bcl-2/Bax expression ratio in rat cortex brain and hippocampus[J].Human&Experimental Toxicology,2017,1(1):81-83.
[7]MUCHMORE S W,SATTLER M,LIANG H,et al.X-ray and NMR structure of human Bcl-x L,an inhibitor of programmed cell death[J].Nature,1996,381(6580):335-341.
[8]YOKOYAMA T,KOHN E,BRILL E,et al.Apoptosis is augmented in high-grade serous ovarian cancer by the combined inhibition of Bcl-2/Bcl-x L and PARP[J].International Journal of Oncology,2017,3(15):455-457.
[9]WIWANITKIT V.Re:Prognostic significance of Bcl-x L gene expression in human colorectal cancer[J].Acta Histochem,2012,114(2):182;author reply 183.
[10]YANG J,SUN M,ZHANG A,et al.Adenovirus-mediated si RNA targeting Bcl-x L inhibits proliferation,reduces invasion and enhances radiosensitivity of human colorectal cancer cells[J].World J Surg Oncol,2011,9:117.
[11]BOLENZ C,BECKER A,TROJAN L,et al.Optimizing chemotherapy for transitional cell carcinoma by application of Bcl-2and bcl-x L antisense oligodeoxynucleotides[J].Urol Oncol,2007,25(6):476-482.
[12]陈寅波,刘卓,钱俊,等.DNA错配修复基因h MLH1与h MSH2在结直肠癌合并慢性血吸虫肠病与散发型结直肠癌中表达的差异研究[J].中华胃肠外科杂志,2016,19(1):75-79.
[13]ZHANG R,TAKAHASHI S,ORITA S,et al.p53 gene mutations in rectal cancer associated with schistosomiasis japonica in Chinese patients[J].Cancer Lett,1998,131(2):215-221.
[14]ZALATA K R,NASIF W A,MING S C,et al.p53,Bcl-2 and C-Myc expressions in colorectal carcinoma associated with schistosomiasis in Egypt[J].Cell Oncol,2005,27(4):245-253.
[15]杨道华,邱承敏,孙玮玮,等.应用组织芯片检测慢性血吸虫病合并大肠癌多基因蛋白的表达[J].中国血吸虫病防治杂志,2014,26(4):405-409.
[16]IMAI J,ICHIKAWA H,MIZUKAMI H,et al.Colonic high-grade tubular adenomas associated with Schistosoma japonicum[J].Tokai J Exp Clin Med,2016,41(1):22-23.
[17]白瑞璞,潘卫庆.日本血吸虫感染小鼠肝脏枯否细胞差异表达Micro RNA及基因的分析[J].中国热带医学,2017,17(4):344-349.
[18]FENG H,LU A G,ZHAO X W,et al.Comparison of nonschistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer[J].World J Gastroenterol,2015,21(23):7225-7232.
[19]张利娟,徐志敏,钱颖骏,等.2015年全国血吸虫病疫情通报[J].中国血吸虫病防治杂志,2016,28(6):611-617.
[20]黎文华,王鹏.干细胞治疗人体寄生虫病研究进展[J].中国血吸虫病防治杂志,2016,28(6):740-744.