奈达铂抑制卵巢癌OVCAR-3细胞增殖及下调Hedgehog信号通路相关蛋白水平

Nedaplatin inhibits ovarian cancer OVCAR-3 cell proliferation and downregulates Hedgehog signaling proteins

目的观察PTCH1在卵巢癌组织中的表达,探讨奈达铂抑制卵巢癌OVCAR-3细胞的增殖以及对Hedgehog信号通路相关蛋白表达的影响。方法应用免疫组织化学染色法检测正常卵巢组织及卵巢癌标本各80例中PTCH1的表达,并观察卵巢癌组织标本中PTCH1表达的规律及其与病理类型、病理分级、淋巴结转移、临床分期、是否行新辅助化疗之间的关系。常规培养卵巢癌细胞OVCAR-3,奈达铂干预后Western blot观察细胞中PTCH1、cyclin D1及Gli1的表达变化情况,CCK-8法检测细胞增殖能力的变化。结果 PTCH1在卵巢癌标本表达率明显高于正常卵巢组织,PTCH1的表达与病理类型、病理分级、淋巴结转移、临床分期无明确联系,但与含奈达铂方案的新辅助化疗的执行相关;奈达铂干预的卵巢癌细胞中PTCH1、cyclin D1及Gli1的表达较未干预组低,其增殖受到明显抑制。结论奈达铂可以通过干扰卵巢癌中Hedgehog通路关键因子从而影响卵巢癌的发生发展。

Objective To invesitgate the expression of PTCH1 in ovarian cancer tissues and the inhibitory effect of nedaplatin on ovarian cancer cell proliferation as well as its influence on the Hedgehog signaling pathways. Methods The expression of PTCH1 in normal ovarian and ovarian cancer tissues （80 cases of each） was detected using immunohistochemical staining. The correlation between PTCH1 expression and tumor pathological type and grade, lymph node metastasis, clinical stage, and neoadjuvant chemotherapy was investigated. In cultured ovarian cancer cells, the expression of PTCH1, Cyclinin1 and Gli1 in response to nedaplatin treatment were further evaluated by Western blotting, and the cell proliferation was determined by CCK-8. Results The expression level of PTCH1 in ovarian cancer was significantly higher than that in normal ovarian tissues, which was not associated with pathological type, pathological grade, lymph node metastasis and clinical stage. However, neoadjuvant chemotherapy reduced the positive expression rate of PTCH1. The expression of PTCH1, CyclinD1 and Gli1 in nedaplatin treated ovarian cancer cells was lower than that in the untreated group. The proliferation of ovarian cancer cells was significantly inhibited after nedaplatin treatment. Conclusion Nedaplatin can affect the development of ovarian cancer by interfering with the key factors of Hedgehog pathway in ovarian cancer.