Department of Pharmacy, People's Hospital of Yuxi City, Yuxi, Yunnan Province, China.
Eur Rev Med Pharmacol Sci. 2017 Sep;21(18):4064-4070.
Gastric cancer is a common malignancy with increasing worldwide incidence, and chemotherapeutic drugs for gastric cancer are not effective. Long non-coding RNA (lncRNA) has been proved to be important in different cancer progression. In this research, we investigated whether lncRNAs have relations with drug resistance in gastric cancer to find new potential targets for therapy, which can increase the survival time of the drug-resistant gastric patient.
qRT-PCR was used to detect the expression of BCAR4 in 113 cases of gastric cancer tissue and adjacent tissue, and the clinical significance was also analyzed. MTT assays and Western blot were performed to cytologically determine the relationship between BCAR4 expression and cisplatin resistance, as well as to investigate the potential molecular mechanism involved.
Compared with the adjacent tissues, we found that BCAR4 was highly expressed in gastric cancer tissues. We also found that the expression of BCAR4 was significantly related to the size of the tumor, clinical classification and the survival time. In cytological experiments, we found the expression of BCAR4 was enhanced in cisplatin-resistant cell strains (SGC7901/DDP). What's more, overexpression of BCAR4 in SGC7901 cells increased resistance to cisplatin while reduced BCAR4 expression increased the sensitivity of SGC7901/DDP cells to cisplatin. Western blot experiments indicated that elevated expression of BCAR4 upregulated tumor stem cell-related biomarkers via regulating Wnt signaling pathway.
We showed that BCAR4 was closely related with the cisplatin-resistant gastric cancer. It might be a promising target for treating gastric cancer and improving the efficiency of chemotherapeutic drugs.
胃癌是一种常见的恶性肿瘤，全球发病率呈上升趋势，且用于胃癌的化疗药物效果不佳。长链非编码 RNA（lncRNA）已被证明在不同癌症的进展中具有重要作用。在这项研究中，我们研究了 lncRNA 是否与胃癌的耐药性有关，以寻找新的治疗靶点，从而延长耐药性胃癌患者的生存时间。
采用 qRT-PCR 检测 113 例胃癌组织及癌旁组织中 BCAR4 的表达，并分析其临床意义。MTT 法和 Western blot 法检测 BCAR4 表达与顺铂耐药性的关系，并探讨其潜在的分子机制。
与癌旁组织相比，我们发现 BCAR4 在胃癌组织中高表达。我们还发现 BCAR4 的表达与肿瘤大小、临床分期和生存时间显著相关。细胞学实验发现，BCAR4 在顺铂耐药细胞株（SGC7901/DDP）中的表达增强。此外，BCAR4 在 SGC7901 细胞中的过表达增加了其对顺铂的耐药性，而降低 BCAR4 的表达则增加了 SGC7901/DDP 细胞对顺铂的敏感性。Western blot 实验表明，BCAR4 的高表达通过调节 Wnt 信号通路上调肿瘤干细胞相关标志物。
我们表明 BCAR4 与顺铂耐药性胃癌密切相关。它可能是治疗胃癌和提高化疗药物疗效的有前途的靶点。
