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Background and purpose:Senescent cancer-associated ifbroblasts (CAFs) in tumor microenvi-ronment are known to mediate the invasion and radio- or chemo-resistance of epithelial cancers. The inflammatory cytokine IL-6 derived from CAFs may promote the invasion and radio-resistance of epithelial cervical cancer. However, the detailed mechanism is not clear. This study aimed to investigate the effects of IL-6 on CAFs senescence, cervical cancer cell invasiveness and radio-resistance.Methods:CAFs from cervical cancer, normal ifbroblasts (NFs) from nor-mal cervical tissues, and cervical cancer cell lines including HeLa, Siha and ME180 were used in this study. Different treatments of cells with IL-6 and inhibitors of STAT3 and Notch were conducted to investigate the alterations of cellular senescence, STAT3/Notch signaling, cell invasiveness, and radiotherapy-induced apoptosis by using cell staining, immunolfuorescence, Western blot, and lfow cytometery.Results:This study found that the conditioned medium (CM) of CAFs or IL-6 could activate the STAT3 and Notch signaling to promote cellular senescence and cervical cancer cell invasiveness. Co-culture of cervical cancer cells HeLa or Siha along with CAFs also increased the invasiveness of can-cer cells, but further treatments of cells by addition of an IL-6 antibody or the inhibitors of STAT3 (S31-201) or Notch (DAPT) blocked the cancer cell invasion. Meanwhile, this study also found that STAT3 functions at the upstream of the Notch signaling to up-regulate Jagged-1, one of the key ligands of Notch in ifbroblasts or epithelial cancer cells through IL-6-mediated autocrine or paracrine pathways, which eventually confers the radio-resistance of cervical cancer cells/tissues.Conclusion:CAFs in tumor microenvironment could induce cervical cancer cell invasiveness and radio-re-sistance through IL-6/STAT3-mediated Notch activation, and that targeting of the STAT3/Notch signaling-associated molecules may improve the effcacy of radiotherapy for cervical cancer.
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AIM: To examine the expression of miRNA-22 in the ovarian tissues and the effect of miRNA-22 over-expression on the proliferation, migration and invasion in SKOV-3 cells.METHODS: The expression levels of miRNA-22 in different ovarian tissues and SKOV-3 cells were determined by qPCR .miRNA-22 was over-expressed by trans-fection of miRNA-22 mimic.The cell viability was examined by CCK-8 assay.The cell migration was measured by wound healing test .The cell invasion was analyzed by Transwell assay .The protein expression levels of VEGF and P 53 were deter-mined by Western blot .RESULTS: Compared with the normal ovarian tissue , the expression level of miRNA-22 was remarkably decreased in the ovarian tumor tissues .After transfection with miRNA-22 mimic, the expression level of miRNA-22 in the SKOV-3 cells was significantly increased , while the cell viability , migration and invasion were obviously decreased .Moreover , the protein expression of VEGF and P 53 was dramatically inhibited after over-expression of miRNA-22.CONCLUSION:The decreased miRNA-22 expression may be correlated with the development of ovarian can-cer.Over-expression of miRNA-22 decreases the cell viability , migration and invasion by reducing the protein expression of VEGF and P53.
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Objective:We aimed to investigate the clinical efficacy of neoadjuvant chemotherapy combined with cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (IHCP) after the operation of patients with advanced ovarian cancer. Meth-ods:Analysis of 60 patients with advanced ovarian cancer was performed at the Zhengzhou People's Hospital from April 2009 to July 2012. The patients were divided into two groups, namely, the research and control groups. The research group was treated with neoadju-vant chemotherapy combined with cytoreductive surgery and IHCP twice (cisplatin at 80 mg), and subsequently, with chemotherapy (TC/TP). The control group underwent primary cytoreductive surgery and chemotherapy (TC/TP). We compared the differences be-tween the two groups in terms of the following parameters:operation time, bleeding volume, volume of ascites, and postoperative che-motherapy. Results:The treatments in the research group were more efficient than those performed on the control group in terms of all the intraoperative indicators, and the difference between the two groups was statistically significant (P<0.05). Conclusion:Compared with conventional methods, the neoadjuvant chemotherapy combined with cytoreductive surgery and IHCP after operation was more ef-fective for patients with advanced ovarian cancer. Thus, neoadjuvant chemotherapy combined with cytoreductive surgery and IHCP af-ter operation can be applied in clinical settings.
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Objective To investigate the distribution of different Human papilloma virus(HPV) subtype infection of women cervixes in parts of Guizhou Province and the high risk factors of HPV infection,in order to offer some evidences for the use of vaccine of cervix eaneers in the region, and offer a group of reliable data for the screen-ing statistics of cervix eaneer in the world. Methods A total of 2339 women having sexual life were checked for 21 HPV genotypes by DNA flow-through hybridization technique and liquid-hased pap test(LPT) in their exfoliated cer-vical cells. Cervix tissues were taken in some HPV positive women and (or) LPT positive women among them for bi-opsy by the vaginoscope. The high risk factors of HPV infection and the distribution feature of HPV subtype infection in the different cervix diseases were anlayzed. Results The total positive rate of HPV infection was 30.31% (709/ 2339 ) in the 2339 women. There were 20 HPV subtypes to be detected. HPV subtype infection from high to low were HPVI6,52,18,58 and 11. The rates of HPV subtype infection were 9.87% (231/2339) ,5.64% ( 132/2339), 4.95% (116/2339 ) ,4.19% (98/2339)and 2.99 % (70/2339). The peak age of HPV infection ranged from 31 to 35 years old. The earlier the first sexual life,the higher HPV infeetion (tendeney X2 test,P <0.05). 366 CIN pa-tients and 181 patients of invasive cervix carcinoma( ICC)were diagnosed through pathology examination. The rate of HPV infection were 34.26% (74/216)in CIN Ⅰ ,77.78% (56/72)in CIN Ⅱ ,82.05% (64/78)in CIN Ⅲ. Among the 181 ICC,the rate of HPV infection was 84.52% (131/155)in squamous carcinoma of the cervix (SCC) and 38.46% (10/26) in adenocareinoma of uterine cervix (AUC). The infeetion rate of HPV16 was 61.83% ( 81/131 ) in the SCC of HPV positive. The infection rate of HPV18 was 60% (6/10)of the AUC of HPV positive. HPV16 was related closely with SCC ( X2 = 11. 948 ,P < 0.001 , ORSCC/AUC = 5. 946). There was no significant difference be-tween HPV 18 in SCC and AUC( P > 0.05). Conclusions The major HPV subtypes are 16,52,18,58 in Guizhou province. There is a close correlation between HPV infection and cervix diseases. HPV infection often occurs in young and middle-aged women. The first sexual life is a high factor of HPV infection. High risk HPV infecting would cause cervix cancer. CIN and cervix cancers are caused by high risk HPV infection. HPV16 is related closely with SCC. There is no significant difference between HPV18 in SCC and AUC. HPV16/18 vaccine could be considered to re-duce the incidence of cervical carcinoma in Guizhou province.