Department of Hepatobiliary Surgery, Sichuan Medical Academy &Sichuan People's Hospital, No 32 Western Third Section of First Ring Road, Chengdu, 610072, Sichuan, China.
Pathol Oncol Res. 2020 Jan;26(1):425-431. doi: 10.1007/s12253-018-0486-5. Epub 2018 Nov 7.
Our study was aimed to identify the fundamental role of lncRNA HOST2 in gemcitabine resistance regulation in human pancreatic cancer cells. The levels of HOST2 in pancreatic cancer cell lines were measured by quantitative real-time PCR (qRT-PCR). Due to high expression and strong gemcitabine resistance, Hs766T and AsPC-1 cell lines were selected to be knockdown the expression of HOST2 by transfection sh-HOST2. After manipulation of HOST2, the cell proliferation induced by gemcitabine was examined by CCK-8 assay. Next, colony formation ability of Hs766T and AsPC-1 cell lines was determined by clone-forming assay. At last, the relationship between HOST2 and cell apoptosis in Hs766T and AsPC-1 cell lines was evaluated by flow cytometry. QRT-PCR revealed that HOST2 was overexpressed in six pancreas neoplasm cell lines compared with normal cell lines HPDE6-C7. HOST2 expression levels in group resistant to gemcitabine were higher than the group sensitive to gemcitabine. Additionally, CCK-8 assay verified that cell proliferation was inhibited by sh-HOST2 with or without gemcitabine treatment. Furthermore, clone-forming assay revealed that colony formation ability was weakened by down-regulated HOST2 with or without gemcitabine treatment. Flow cytometry revealed that cell apoptosis induced by gemcitabine was promoted by sh-HOST2. In conclusion, down-regulated HOST2 inhibited proliferation and promoted apoptosis of pancreas cancer cells with or without gemcitabine treatment. Thus, HOST2 is a potential therapeutic target for gemcitabine chemoresistance in pancreatic neoplasms.
我们的研究旨在确定 lncRNA HOST2 在人胰腺癌细胞中对吉西他滨耐药调节的基本作用。通过实时定量 PCR(qRT-PCR)测量胰腺癌细胞系中 HOST2 的水平。由于高表达和强吉西他滨耐药性,选择 Hs766T 和 AsPC-1 细胞系通过转染 sh-HOST2 敲低 HOST2 的表达。操纵 HOST2 后,通过 CCK-8 测定法检查吉西他滨诱导的细胞增殖。接下来,通过克隆形成测定法测定 Hs766T 和 AsPC-1 细胞系的集落形成能力。最后,通过流式细胞术评估 HOST2 与 Hs766T 和 AsPC-1 细胞系中细胞凋亡的关系。QRT-PCR 显示,与正常细胞系 HPDE6-C7 相比,六株胰腺肿瘤细胞系中 HOST2 表达过度。对吉西他滨耐药的组中 HOST2 的表达水平高于对吉西他滨敏感的组。此外,CCK-8 测定法证实,sh-HOST2 处理或不处理吉西他滨均可抑制细胞增殖。此外,克隆形成测定法显示,下调 HOST2 处理或不处理吉西他滨均可减弱集落形成能力。流式细胞术显示,sh-HOST2 可促进吉西他滨诱导的细胞凋亡。总之,下调 HOST2 抑制了胰腺癌细胞的增殖并促进了其凋亡,无论是否用吉西他滨处理。因此,HOST2 是胰腺肿瘤中吉西他滨化疗耐药的潜在治疗靶标。