[PubMed] [Google Scholar] 12. 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. ValueValueValue

Tumor size3.560.01Lymph node metastasis4.860.02Distant metastasis5.180.01TNM stage3.870.01VASH2 levels4.120.01 Open in a separate window Promoting Effects of VASH2 on NSCLC Cell Proliferation and Resistance to Doxorubicin We then studied the effects of VASH2 on NSCLC cell proliferation 3PO and resistance to doxorubicin. We found that the expression levels of VASH2 were significantly increased in NSCLC cells (A549 and H358) compared with normal cell line BEAS-2B (Fig. 2A and B). The expression levels of VASH2 in H358 were higher than in A549 cells (Fig. 2A and B). As expected, the inhibition rates in H358 were lower than in A549 when the cells were treated with ADR; thus, the IC50 of H358 was higher than that of A549 (Fig. 2C and D). A549 cells were transfected with VASH2 expression plasmid to upregulate its expression. After transfection, the VASH2 levels were upregulated in the VASH2 group compared to the blank group (Fig. 3A and B). We then found that overexpression of VASH2 enhanced the protein expression of P-glycoprotein (Fig. 3B) in NSCLC cells. Moreover, VASH2 upregulation significantly reduced the inhibition rate (IR) of cells in doxorubicin (Fig. 3C), and the IC50 of doxorubicin was significantly increased (Fig. 3D). These findings suggest that VASH2 is associated with doxorubicin resistance in NSCLC cells. Open in a separate window Figure 2 The VASH2 expression in NSCLC cell lines. (A) RT-PCR was performed to measure the expression of VASH2 in NSCLC cell lines (A549 and H358) and the normal cell line BEAS-2B. (B) Western blot was performed to measure the expression of VASH2 in NSCLC cell lines (A549 and H358) and the normal cell line BEAS-2B. (C) MTT assay was performed to measure the inhibition rate in A549 and H358 cells after doxorubicin treatment (2, 4, 8, 16, or 32 mol/L). (D) The half 3PO maximal inhibitory concentration (IC50) was calculated from (C). *p?p?VHL has promoting effects on NSCLC cell proliferation and resistance to doxorubicin. VASH2 Is Upregulated in Established Doxorubicin-Resistant NSCLC Cells To further confirm that VASH2 is involved in the resistance of NSCLC cells to doxorubicin, two doxorubicin-resistant NSCLC cell lines were established. The established A549-doxorubicin (Fig. 4A and B) and H358-doxorubicin cells (Fig. 4E and F) showed reduced IR and increased IC50 in doxorubicin. Moreover, the mRNA and protein levels of VASH2 were significantly increased in doxorubicin-resistant NSCLC cells (Fig. 4C, D, G, and H). These findings further suggest.