Open AccessVASH2 Promotes Cell Proliferation and Resistance to Doxorubicin in Non-Small Cell Lung Cancer via AKT Signaling
Author(s) -
Xiangbin Tan,
Ze-fei Liao,
Shuangyou Zou,
Liangyun Ma,
Aimin Wang
Publication year - 2020
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504019x15509383469698
Subject(s) - protein kinase b , cancer research , cell growth , doxorubicin , downregulation and upregulation , signal transduction , cell culture , gene knockdown , ly294002 , lung cancer , chemistry , biology , medicine , microbiology and biotechnology , chemotherapy , biochemistry , genetics , gene
Vasohibin2 (VASH2), a proangiogenic factor, has been demonstrated to play an oncogenic role in some common human cancers. However, the detailed function of VASH2 in non-small cell lung cancer (NSCLC) has not previously been studied. In this study, we found that VASH2 was significantly upregulated in NSCLC tissues and cell lines, and its increased expression was associated with NSCLC progression and poor prognosis of patients. Knockdown of VASH2 markedly inhibited cell proliferation and P-glycoprotein expression in NSCLC cells. Overexpression of VASH2 enhanced cell proliferation, P-glycoprotein expression, as well as doxorubicin resistance in NSCLC cells. Moreover, the expression levels of VASH2 were significantly increased in newly established doxorubicin-resistant NSCLC cells. Molecular mechanism investigation revealed that inhibition of VASH2 expression in NSCLC cells suppressed the activity of AKT signaling, and overexpression of VASH2 enhanced the activity of AKT signaling. We further showed that downregulation of AKT signaling activity using AKT inhibitor LY294002 markedly inhibited NSCLC cell proliferation and resistance to doxorubicin induced by VASH2. In conclusion, the findings in the present study indicate that VASH2 promotes NSCLC cell proliferation and resistance to doxorubicin via modulation of AKT signaling. Thus, we suggest that VASH2 may become a potential therapeutic target for the treatment of NSCLC.