Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu City, China.
J Cell Mol Med. 2019 Jan;23(1):656-669. doi: 10.1111/jcmm.13970. Epub 2018 Oct 19.
This study was implemented to figure out whether lncRNA HOTAIR/miR-17-5p/PTEN axis played a role that was opposite to Shenqifuzheng (SQFZ) injection in regulating the chemosensitivity of gastric cancer cells. The gastric cancer tissues were gathered and four gastric cancer cell lines were prepared, including BGC-823, MGC-803, SGC-7901, and MKN28. Moreover, cisplatin, adriamycin, mitomycin, and 5-fluoroura were managed as the chemo-therapeutics, and SQFZ was prepared as a Chinese medicine. Striking distinctions of HOTAIR, miR-17-5p, and PTEN expressions were observed between gastric cancer tissues and para-carcinoma normal tissues (P < 0.05). MKN28 was associated with the highest resistance to cisplatin, adriamycin, mitomycin, and 5-fluoroura among all the cell types, and SQFZ significantly improved the MKN28 cells' sensitivity to the drugs (P < 0.05). The over-expressed HOTAIR and miR-17-5p, as well as under-expressed PTEN tended to significantly facilitate the viability, EMT process and proliferation of MKN28 cells that were subject to treatment of chemo-therapies (P < 0.05). SQFZ could amplify the effects of si-HOTAIR, miR-17-5p inhibitor, and pcDNA-PTEN on boosting the chemosensitivity of gastric cancer cells (P < 0.05). In addition, HOTAIR was also found to directly target miR-17-5p, and PTEN appeared to be subject to the modification of HOTAIR and miR-17-5p in its acting on the viability, proliferation, EMT process, and apoptosis of gastric cancer cells. The HOTAIR/miR-17-5p/PTEN axis could be regarded as the potential treatment targets for gastric cancer, and adjuvant therapy of SQFZ injection could assist in further improving the treatment efficacy of chemo-therapies for gastric cancer.
本研究旨在探讨长链非编码 RNA HOTAIR/miR-17-5p/PTEN 轴是否在调节胃癌细胞化疗敏感性方面发挥与参芪扶正注射液（SQFZ）相反的作用。收集胃癌组织，制备 4 种胃癌细胞系，包括 BGC-823、MGC-803、SGC-7901 和 MKN28。此外，顺铂、阿霉素、丝裂霉素和 5-氟尿嘧啶被用作化疗药物，SQFZ 被制备成中药。胃癌组织和癌旁正常组织中 HOTAIR、miR-17-5p 和 PTEN 的表达存在显著差异（P<0.05）。在所有细胞类型中，MKN28 对顺铂、阿霉素、丝裂霉素和 5-氟尿嘧啶的耐药性最高，SQFZ 显著提高了 MKN28 细胞对药物的敏感性（P<0.05）。过表达 HOTAIR 和 miR-17-5p 以及下调 PTEN 倾向于显著促进化疗药物处理后的 MKN28 细胞的活力、EMT 过程和增殖（P<0.05）。SQFZ 可增强 si-HOTAIR、miR-17-5p 抑制剂和 pcDNA-PTEN 对提高胃癌细胞化疗敏感性的作用（P<0.05）。此外，还发现 HOTAIR 可直接靶向 miR-17-5p，而 PTEN 似乎受到 HOTAIR 和 miR-17-5p 的修饰，从而影响胃癌细胞的活力、增殖、EMT 过程和凋亡。HOTAIR/miR-17-5p/PTEN 轴可作为胃癌的潜在治疗靶点，SQFZ 注射液辅助治疗可进一步提高胃癌化疗疗效。
