PTX3在人類子宮頸癌細胞之角色

子宮頸癌是婦女中最常見的癌症之一，與高危險性的人類乳突病毒(HPV, Human Papilloma Virus)感染有關。子宮頸癌造成許多台灣婦女死亡，如果我們能有效地治療子宮頸癌，將可大幅地降低癌症死亡率。PTX3( Pentraxin 3) 五聚環蛋白相關蛋白PTX3也稱為腫瘤壞死因子誘導性基因14蛋白（TSG-14）基因位於染色體3（q24-28）是五聚環蛋白超家族的成員之一，屬於發炎蛋白之一，已知可能參與細胞凋亡和分化作用，但PTX3在人類子宮頸癌扮演的角色仍不清楚。 本研究利用人類子宮頸癌組織晶片以化學免疫染色法分析證實人類子宮頸癌組織內PTX3蛋白表現比正常子宮頸組織還高。為了釐清PTX3人類子宮頸癌細胞的表現，利用西方墨點法發現PTX3在高度惡化 (Hela及SiHa)細胞中比低度惡化(C33A)細胞表現還高。為了證實PTX3在子宮頸癌的生物功能，我們利用shLuc和shPTX3分別感染Hela與SiHa細胞來抑制內生性PTX3蛋白，分別以MTT、流式細胞儀和西方墨點法證實抑制PTX3降低細胞生長、誘導細胞週期G2/M停滯，同時也證實抑制PTX3會抑制細胞週期蛋白cyclin B1、cdc2 和 cdc25c，且增加 p-cdc2、p-cdc25c、p21和p27 蛋白表現。另外我們也證實抑制PTX3會抑制子宮頸癌細胞移動與侵襲，同時抑制PTX3也會降低MMP-2、MMP-9與uPA蛋白量。綜合以上實驗結果說明PTX3在子宮頸癌癌的增生與侵襲中扮演了一個重要的角色，且可當作子宮頸癌進展的指標蛋白。

Cervical carcinoma is one of the most frequent cancers in women and is associated with high-risk human papilloma virus (HPV) infection. It causes many women death in Taiwan. PTX3 also called tumor necrosis factor-inducible protein 14 gene (TSG-14) were mapped to chromosomes 24q28.3. PTX3 regulate cell growth, differentiation, invasion and apoptosis have been reported. However, its involvement in human cervical cancer progression remains unclear. In our study, Using human cervical cancer tissues array, we found that expression level of PTX3 is higher in human cervical cancer tissues than that is human normal cervical tissues. We also found that PTX3 protein expression is higher in high malignant Hela and SiHa cells than in low malignant C33A cells. To verify the biological function of PTX3 in cervical cancer cells, we constructed Lentivirus-mediated PTX3 interference and found growth retargation of cervical cancer assessed by the MTT assay. Likewise, inhibition of PTX3 expression induced cell-cycle arrest in Hela and SiHa cells by up-regulating the expression of p-cdc25c, p-cdc2, p21 and p27, down-regulating the expression of cyclin B1、cdc2 and cdc25c protein expressions. Knockdown of PTX3 decreased migration and invasion in HeLa and SiHa cells, and down-regulation of MMP-2, MMP-9 and u-PA. Our results suggest that PTX3 plays an important role in regulation of proliferation and invasion of human cervical cancer, and it can be a valuable marker in detecticy cervical cancer progression. Therefore, PTX3 is a master regulator of human cervical growth, being an useful in easlier predicting target for cervical cancer prognosis.