Lentivirus‑mediated CD44s expression increases human basal cell carcinoma cell resistance against vismodegib

慢病毒介导的 CD44s 表达增强人类基底细胞癌细胞对 vismodegib 的耐药性

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作者:Jianwen Ren, Xiaona Ma, Chen Tu, Zhangjun Li

Abstract

High drug resistance, which is usually mediated by drug resistance‑associated genes, is a characteristic of human tumours. CD44s, an ATP‑binding cassette multidrug resistance transporter, is expressed in a variety of human cancers. In the present study, the effect of CD44s expression was investigated on BCC resistance against vismodegib. Lentiviral vectors were constructed to allow efficient CD44s expression. Cell clones expressing the CD44s construct were selected and expanded and then identified using qRT‑PCR and western blotting. A lentiviral vector containing a blank sequence was used as a control. Cellular growth capacity and cell sensitivity to vismodegib were detected by MTT and Transwell assays, respectively. BCC cell growth was evaluated in vivo with a transplanted BCC nude mouse model. The cell clones expressing CD44s at high levels were identified by qRT‑PCR and western blotting, and the difference in the cell proliferation rate between these cells and LV‑CON BCC cells was assessed by growth curve analysis. The in vitro study revealed that treatment with vismodegib decreased BCC cell growth and migration; however, these effects were reversed by LV‑CD44s overexpression. The in vivo study revealed that BCC tumour growth was significantly increased in nude mice transplanted with cells stably infected with CD44s compared with nude mice transplanted with cells infected with a control vector. Our investigation demonstrated that lentivirus‑mediated CD44s expression may reverse the effects of vismodegib treatment on BCC.

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