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

Ren,Jianwen; Ma,Xiaona; Tu,Chen; Li,Zhangjun

doi:10.3892/or.2020.7534

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

Authors:
- Jianwen Ren
- Xiaona Ma
- Chen Tu
- Zhangjun Li
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Affiliations: Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710014, P.R. China, Department of Dermatology, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi 716000, P.R. China
Published online on: March 6, 2020 https://doi.org/10.3892/or.2020.7534
Pages: 1650-1658

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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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