Bleomycin Suppresses the Proliferation and the Mobility of Human Gastric Cancer Cells Through the Smad Signaling Pathway
Bleomycin Suppresses the Proliferation and the Mobility of Human Gastric Cancer Cells Through the Smad Signaling Pathway
复制标题
博来霉素通过 Smad 信号通路抑制人胃癌细胞的增殖和迁移。
DOI：
10.1159/000453192
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发表时间：
2016-01-01
影响因子：
--
通讯作者：
Xu, Xiao-yan
中科院分区：
文献类型：
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作者：
Liu, Jin-fang;Nie, Xiao-cui;Xu, Xiao-yan
背景/目的：广泛的研究表明，博莱霉素（BLM）是一种糖肽抗生素，已被用作抗癌化疗试剂。它能诱导癌细胞单链和双链DNA损伤，抑制DNA合成，抑制增殖，诱导细胞凋亡。Smad信号转导被认为是肿瘤发生发展的重要分子，可能与包括胃癌在内的一些恶性肿瘤的生物学行为密切相关。方法：采用CCK-8法、Annexin V/PI双染色法、PI染色法和transwell法检测不同浓度BLM对胃癌细胞株MKN45和AGS增殖、细胞周期、凋亡、迁移和侵袭的影响。应用Western blot和免疫组织化学分析其可能的作用机制。结果：BLM处理使MKN45和AGS细胞增殖低、凋亡高、迁移和侵袭低。此外，Smad3与BLM结合后活性发生改变的可能机制，随后Smad信号通路发生级联反应。结论：BLM是胃癌治疗的一个令人兴奋的主题，可能是一种有效的胃癌患者临床治疗试剂。
Background/Aims: Extensive studies have demonstrated that Bleomycin (BLM) is a glycopeptide antibiotic that has been used as an anticancer chemotherapeutic reagent. It can induce both single- and double-strand DNA damage, inhibit synthesis of DNA, suppress proliferation, and induce apoptosis in cancer cells. Smad signaling transducers are considered as important molecules in tumor development and progression, and may closely be related to the biological behaviors of some malignant carcinomas, including gastric cancer. Methods: The effects of different concentrations of BLM on the proliferation, cell cycle, apoptosis, migration, and invasion on gastric cancer cell lines MKN45 and AGS were assayed by using CCK-8 assay, Annexin V/PI double staining, PI staining, and transwell assay. Western blot and Immunohistochemistry were applied to analyze the potential mechanism(s). Results: BLM treatment resulted in a low proliferation, high apoptosis, low migration and invasion in MKN45 and AGS cells. Furthermore, the possible mechanisms underlying that Smad3 activity could be changed after binding with BLM, and subsequently the Smad signaling pathway had a cascade response. Conclusion: These results highlight BLM as an exciting theme for gastric cancer treatment, which may represent an effective clinical therapeutic reagent for gastric cancer patients.