Cyclo-oxygenase-2 promotes migration and invasion of breast cancer MDA-MB231 cells by regulating EMT / 中国肿瘤生物治疗杂志

@#Objective:To investigate the role of cyclo-oxygenase-2 (COX-2) in breast cancer metastasis and its possible mechanism. Methods: A total of 45 cases of primary breast cancer tissues and brain metastatic breast cancer tissues were collected from patients, who underwent mastectomy in Yunnan Cancer Hospital from October 2015 to April 2018, including 30 cases of primary lesions and 15 cases of brain metastasis. qPCR was used to detect the expression of COX-2 in breast cancer tissues and brain metastatic breast cancer tissues. Recombinant viruses with COX-2 over-expression (LV6-COX2) or COX-2 knockdown (LV3-COX2 shRNA1, LV3-COX2 shRNA2) were transfected into human breast cancer MDA-MB-231 cells; After obtaining the stable expression cell lines, the effect of COX-2 expression on the proliferation of MDA-MB-231 cells was detected by CCK-8, and the effects of COX-2 expression on the migration and invasion of MDA-MB-231 cells were detected by scratch test and Transwell assay, respectively. The mRNAand protein expressions of COX-2 in each group were examined by qPCR and WB, respectively. The effect of COX-2 expression on the expression of EMT-related genes in MDA-MB-231 cells was analyzed by qPCR. Results: The expression of COX-2 in tissues of patients with brain metastases was significantly higher than that in patients with primary breast cancer tissues (P<0.01), and it was correlated with tumor TMN stage in breast cancer patients. MDA-MB-231 cell lines with stable COX-2 over-expression/knockout were successfully constructed. Over-expression of COX-2 promoted the migration and invasion of MDA-MB-231 cells (all P<0.01), and significantly increased the expressions of MMP2, MMP1, N-cadherin and vimentin (all P<0.01), but exerted insignificant effect on cell proliferation. The effect of COX-2 silence exerted the opposite effect and promoted cell proliferation (P<0.05). Conclusion: COX-2 is highly expressed in brain metastatic breast cancer tissues, which may promote the migration and invasion of breast cancer MDA-MB-231 cells by regulating EMT processes.

Influencing factors of therapeutic effect of immunologic checkpoint inhibitors on cancer / 中国肿瘤生物治疗杂志

@# 肿瘤免疫治疗主要通过调节机体免疫和肿瘤之间的平衡来实现肿瘤治疗的目的，已证实对多种肿瘤具有显著的临床 疗效，被认为是继手术、化疗、放疗后又一重要的治疗方法。但目前肿瘤免疫治疗尚无统一的临床应用方案，对不同的肿瘤或同 一肿瘤的不同个体疗效差异巨大，严重制约其发展。既往研究发现,影响免疫检查点抑制剂反应和耐药性的关键因素包括肿瘤本 身的特征（如癌症基因组、表观基因组和微环境）、肿瘤免疫表型、宿主免疫组分（全身免疫和抗肿瘤免疫）及其他的外部影响。然 而，最新研究表明，肿瘤突变负荷、DNA修复基因、HLA基因型、PD-L1表达以及肿瘤免疫抑制微环境与免疫检查点抑制剂的反 应密切相关。因此，本文将从肿瘤突变负荷、DNA修复基因、HLA基因型、PD-L1表达以及肿瘤免疫抑制微环境等5个方面阐述 其影响免疫检查点抑制剂的新机制，旨在为肿瘤的靶向治疗提供借鉴。