Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213161, China.
Biosci Rep. 2020 Jul 31;40(7). doi: 10.1042/BSR20201627.
Drug resistance of Taxol leads to the treatment failure in hepatocellular carcinoma (HCC). LncRNA HOTAIR have drawn increasing attention in various diseases; its function and mechanism in Taxol-resistance in HCC remain unclear. In the present study, the two Taxol resistant HCC cell lines (HepG2/Taxol and SMMC7721/Taxol) were induced. The qRT-PCR data exhibited that over-expressed HOTAIR as well as low-expressed miR-34a were founded in HepG2/Taxol and SMMC7721/Taxol cells. HOTAIR knockdown suppresses proliferation, invasion and promotes apoptosis of in HepG2/Taxol and SMMC7721/Taxol cells through up-regulating miR-34a by MTT assay, transwell invasion assays and flow cytometry, while down-regulation of miR-34a had an opposite effect on reversing Taxol resistance. Cleaved caspase-3 and Bax were significantly up-regulated by si-HOTAIR transfection, while Bcl-2 level exhibited opposite trend. Besides, HOTAIR knockdown impaired Taxol-resistance in HCC by accommodating Akt phosphorylation and Wnt/β-catenin signaling via interacting with miR-34a. The present study may afford a valuable target for treating Taxol-resistance in HCC.
紫杉醇耐药导致肝细胞癌 (HCC) 治疗失败。LncRNA HOTAIR 在各种疾病中引起了越来越多的关注；其在 HCC 紫杉醇耐药中的功能和机制尚不清楚。在本研究中，诱导了两种紫杉醇耐药 HCC 细胞系（HepG2/Taxol 和 SMMC7721/Taxol）。qRT-PCR 数据显示，在 HepG2/Taxol 和 SMMC7721/Taxol 细胞中发现了高表达的 HOTAIR 和低表达的 miR-34a。通过 MTT 测定、Transwell 侵袭实验和流式细胞术，HOTAIR 敲低通过上调 miR-34a 抑制 HepG2/Taxol 和 SMMC7721/Taxol 细胞的增殖、侵袭并促进凋亡，而下调 miR-34a 则对逆转紫杉醇耐药有相反的作用。si-HOTAIR 转染后，cleaved caspase-3 和 Bax 明显上调，而 Bcl-2 水平呈相反趋势。此外，HOTAIR 敲低通过与 miR-34a 相互作用，阻碍了 Akt 磷酸化和 Wnt/β-catenin 信号通路，从而损害了 HCC 的紫杉醇耐药性。本研究可为治疗 HCC 紫杉醇耐药提供有价值的靶点。
