Correlations of MicroRNA-21 Gene Polymorphisms With Chemosensitivity and Prognosis of Cervical Cancer.

BACKGROUND: We investigated correlations of miR-21 gene polymorphisms including rs1292037 (A > G) and rs13137 (A > T) with the chemosensitivity to cisplatin plus paclitaxel, and prognosis before cervical cancer (CC) surgery, which may provide a novel target for prevention and treatment of CC. MATERIALS AND METHODS: A total of 165 patients with CC were divided into 2 groups, a sensitive group and resistance group. Gene polymorphisms of rs1292037 (A > G) and rs13137 (A > T) were detected respectively. Logistic and Cox multivariate regression analyses were used to explore factors that influence resistance to cisplatin plus paclitaxel. RESULTS: rs1292037 (A > G) locus AG, GG, AG + GG and G allele in miR-21 gene may increase chemoresistance to cisplatin plus paclitaxel in CC. The risk factors of prognosis included rs1292037 (A > G) locus, tumor stage, maximum lesion diameter and lymph node metastasis (hazard ratio [HR] = 1.819, 95% CI = 1.127-2.935; HR = 1.504, 95% CI = 1.070-2.114; HR = 1.671, 95% CI = 1.038-2.689; HR = 3.043, 95% CI = 1.783-5.193). The influencing factors of resistance to cisplatin plus paclitaxel included maximum lesion diameter, tumor stage, lymph node metastasis and rs1292037 (odds ratio [OR] = 14.047, 95% CI = 5.694-34.653; OR = 5.873, 95% CI = 3.104-11.110; OR = 3.574, 95% CI = 1.554-8.216; OR = 2.449, 95% CI = 1.052-5.705). CONCLUSIONS: rs1292037 (A > G) locus are associated with the chemoresistance to cisplatin plus paclitaxel and prognosis of patients with CC. In addition to that, the G allele at rs1292037 (A > G) locus increases the risk of preoperative chemoresistance to cisplatin plus paclitaxel and is a poor prognostic factor for patients with CC.

[Th1/Th2 and Treg/Th17 cell balance in peripheral blood of patients with ovarian cancer].

OBJECTIVE: To investigate the changes in the percentages and balance of CD4+T cell subsets including T helper cells (Thl, Th2, and Thl7) and T regulatory cells (Treg) in patients with ovarian cancer. METHODS: Peripheral blood samples were collected from 30 patients with ovarian cancer and 20 healthy subjects for analysis of the percentages of Thl, Th2, Thl7 and Treg using flow cytometry. RESULTS: Compared with the control subjects, the patients with ovarian cancer showed significantly increased percentages of Th2, Thl7 and Treg (P<0.05) but significantly decreased percentage of Th1 in the peripheral blood of patients with ovarian cancer (P<0.05). The changes in CD4+ T cell subsets were significantly correlated with the clinical stage of the tumor (P<0.05) but not with the histological type or cell differentiation (P>0.05). The Th1/Th2 ratio was significantly decreased in ovarian cancer patients (P<0.05) with obvious Th2 polarization compared with control group. The Treg/Th17 ratio was significantly increased in ovarian cancer patients (P<0.05). CONCLUSION: Patients with in ovarian cancer have abnormal expressions of CD4+T cell subsets in the peripheral blood with Th1/Th2 and Treg/Th17 imbalance, and these findings provide evidence for clinical immunotherapy of ovarian cancer.

HSP70 inhibitor combined with cisplatin suppresses the cervical cancer proliferation in vitro and transplanted tumor growth: An experimental study.

OBJECTIVE: To study the regulating effect of HSP70 inhibitor (PES) combined with cisplatin on cervical cancer proliferation in vitro and transplanted tumor growth. METHODS: Cervical cancer Hela cell lines were cultured and divided into control group, cisplatin group, PES group and cisplatin + PES group that were treated with serum-free DMEM, cisplatin with final concentration of 10 µmol/L, PES 20 µmol/L and cisplatin 10 µmol/L combined with PES with 20 µmol/L, respectively; animal models with cervical cancer xenografts were established and divided into control group, cisplatin group, PES group and cisplatin + PES group who received intra-tumor injection of normal saline, 10 µmol/L cisplatin, 20 µmol/L PES as well as 10 µmol/L cisplatin + 20 µmol/L PES, respectively. Cell proliferation activity, transplanted tumor volume and mitochondria apoptosis molecule expression were detected. RESULTS: Cell viability value and Bcl-2 mRNA expression in cells of cisplatin group, PES group and cisplatin + PES group were significantly lower than those of control group while Bax, Caspase-3 and Caspase-9 mRNA expression in cells were significantly higher than those of control group; transplanted tumor volume and the Bcl-2 mRNA expression in transplanted tumor tissue of cisplatin group, PES group and cisplatin + PES group were significantly lower than those of control group while Bax, Caspase-3 and Caspase-9 mRNA expression in transplanted tumor tissue were significantly higher than those of control group. CONCLUSIONS: HSP70 inhibitor combined with cisplatin can inhibit cervical cancer cell proliferation in vitro and transplanted tumor growth through mitochondrial apoptosis pathway.

Expression and mechanism of action of miR-196a in epithelial ovarian cancer.

OBJECTIVE: To explore the expression, biological function and possible mechanism of action of microRNA molecular-196a (miR-196a) in epithelial ovarian cancer. METHODS: RT-PCR was used to detect the expression quantities of epithelial ovarian tissue, benign ovarian tissue, normal ovary epithelial tissue, ovarian cancer cell lines and miR-196a in normal ovarian epithelial cells to analyze the relationship between the expression of miR-196a and the clinical pathologic parameters of ovarian cancer. Among those cell lines, the cell line of which miR-196a expressed the most or least was selected and transfected the ovarian cancer cell line by using negative control plasma and miR-196a inhibitor. After transfection, RT-PCR was used to test the expression quantity of miR-196a, Transwell chamber method was applied to determine the migration and invasion abilities of ovarian carcinoma cells and Western blot was employed to detect the expression of HOXA10 protein. RESULTS: The relative expression quantities of miR-196a in ovarian cancer tissue and benign ovarian tissue were significantly higher than that in normal ovarian epithelial tissue, and the expression quantity of miR-196a in ovarian cancer tissue was distinctively higher than that in benign ovarian tissue (P < 0.05). Among 78 cases of epithelial ovarian cancer, the expression quantities of miR-196a in patients with low differentiation were all significantly higher than those in patients with high differentiation (P < 0.05). The expression of miR-196a showed no significant relation with age, clinical stage and whether CA125 was positive or not in patients (P > 0.05). Compared with normal ovarian epithelial cell line IOSE80, the expression quantities of miR-196a of all ovarian cancer cell lines increased obviously and differences were statistically significant (P < 0.05). Among them, the expression of miR-196a of ovarian cancer cell line SKOV3 was the highest, while it decreased significantly (4.678 ± 0.785 vs. 2.131 ± 0.345, t = 2.938, P < 0.05) after the ovarian cancer cell line SKOV3 was transfected by miR-196a inhibitor. The results of Transwell chamber method showed that the migration and invasion abilities of ovarian cancer cells SKOV3 were declined significantly after the expression of miR-196a was down-regulated and the difference showed statistical significance (P < 0.05). The results of Western blot revealed that the relative expression of HOXA10 decreased distinctly after the expression of miR-196a was down-regulated and also the difference showed statistical significance (P < 0.05). CONCLUSIONS: The miR-196a might serve as a cancer-promoting gene to promote the migration and invasion of epithelial ovarian cancer by downstream target gene HOXA10.

[Inhibiting HSP70 expression enhances cisplatin sensitivity of cervical cancer cells].

OBJECTIVE: To investigate the relationship between sensitivity to cisplatin (DDP) and the expression of HSP70 in cervical cancer cells in vitro. METHODS: Cervical cancer Hela229 cells treated with different concentrations of DDP and the HSP70 inhibitor (PFT-µ) were examined for cell viability using MTT assay and colony forming ability. The cell apoptosis was analyzed by flow cytometry with propidium iodide staining and DAPI staining, and JC-1 staining was used to determine mitochondrial membrane potential. The expressions of HSP70, Bcl-2, Bax and caspase-3 were measured with Western blotting. A nude mouse model bearing Hela229 cell xenograft was used to evaluate the effect of DDP and PFT-µ on tumor growth. RESULTS: Hela229 cells expressed a higher level of HSP70 than normal cervical cells. The combined use of PFT-µ significantly enhanced the inhibitory effect of DDP (P<0.01) and increased the cell apoptosis in Hela229 cells. JC-1 staining demonstrated that DDP combined with PFT-µ more obviously reduced mitochondrial membrane potential. DDP combined with PFT-µ more strongly lowered Bcl-2 expression and increased the expressions of casepase-3 and Bax than DDP alone. In the nude mouse model, PFT-µ significantly enhanced DDP sensitivity of Hela229 cell xenografts (P<0.01). CONCLUSIONS: Inhibition of HSP70 expression can enhance the sensitivity of cervical cancer cell to DDP both in vivo and in vitro possibly by promoting cell apoptosis, suggesting the potential of HSP70 as a new target for gene therapy of cervical cancer.

[Expression and clinical significance of phosphatidylinositol 3-kinase and protein kinase B in cervical carcinoma].

BACKGROUND & OBJECTIVE: Phosphatidylinositol 3-kinase /protein kinase B (PI3K/Akt) signaling pathway is involved in a variety of important cellular functions, including genesis and progression of neoplasms. However, its role in cervical cancer is unclear. This study was to detect the expression of PI3K and Akt proteins in different cervical lesions, and to investigate the correlation of PI3K/Akt signal transduction pathway to biological behaviors of cervical carcinoma. METHODS: The expression of PI3K and Akt in 76 specimens of cervical carcinoma,21 specimens of cervical intraepithelial neoplasia and 10 specimens of normal cervical epithelium were detected by SP immunohistochemistry. Their correlations to clinicopathologic features of cervical carcinoma were analyzed. RESULTS: The positive rates of PI3K and Akt were significantly lower in normal cervical epithelium and cervical intraepithelial neoplasia than in cervical carcinoma (0.0% and 42.9% vs. 69.7%, P<0.01;10.0% and 52.4% vs. 75.0%,P<0.01). The expression of PI3K and Akt proteins were correlated to clinical stage, pathologic grade and lymph node metastasis(P<0.01), but not to age, the size of primary focus, and histological type(P>0.05).The expression of PI3K protein was positively correlated to the expression of Akt protein(r=0.425,P<0.01). CONCLUSION: High expression of PI3K and Akt are involved in proliferation, malignant transformation, invasion and metastasis of cervical carcinoma, both of which may play important roles in the occurrence and development of human cervical carcinoma.