Effect of lncRNA LINC00958 on Apatinib Resistance in Small Cell Lung Cancer

This work aimed to study the effect and mechanism of lncRNA LINC00958 on the AP (apatinib) resistance of small cell lung cancer cells. The method of gradually increasing the concentration of apatinib was used to establish a small cell lung cancer cell line H446/AP resistant to apatinib, H446 and H446/AP cells were treated with 2.5 μmol/L, 5 μmol/L, 10 μmol/L, 20 μmol/L, 40 μmol/L apapitinib to detect the inhibition rate of proliferation. Then the H446/AP cells were divided into AP+si-NC group (transfected with LINC00958 interference vector negative control+5 μmol/L apatinib), AP+si-LINC00958 group (transfected with LINC00958 interference vector+5 μmol/L apatinib), AP+miR-NC group (transfected miR-490-3p mimic negative control+5 μmol/L apatinib), AP+miR-490-3p group (transfected miR-490-3p mimetic+5 μmol/L apatinib), AP+si-LINC00958+anti-miR-NC group (cotransfected with LINC00958 interference vector and miR-490-3p inhibitor vector negative control+5 μmol/L apatinb), AP+si-LINC00958+anti-miR-490-3p group (cotransfected with LINC00958 interference vector and miR-490-3p suppression vector+5 μmol/L apatinib). RT-qPCR (real-time quantitative PCR) was used to detect the expression of LINC00958 and miR-490-3p; CCK-8 (cell counting kit 8) was used to detect the inhibition rate of cell proliferation; Western blot was used to detect protein expressions; Scratch test to detect cell scratch healing rate; Transwell was used to detect cell migration and invasion; dual luciferase reporter assay was used to detect the targeting relationship between LINC00958 and miR-490-3p. The results show that LINC00958 was highly expressed in small cell lung cancer tissues, and miR-490-3p was lowly expressed (P<0.05). Compared with H446 cells, the expression of LINC00958 in H446/AP cells was significantly increased, while the expression of miR-490-3p was significantly decreased (P<0.05). After treatment with different concentrations of apatinib, the proliferation inhibition rate of H446/AP cells was significantly decreased compared with H446 cells, while IC50 (half inhibitory concentration) was significantly increased (P<0.05). For inhibition of LINC00958 expression combined with apatinib and miR-490-3p overexpression combined with apatinib, CyclinD1, MMP-2, MMP-9 expression were significantly decreased in H446/AP cells; p21 expression was significantly increased in H446/AP cells, and H446/AP cell inhibition rate was significantly increased; scratch healing rate was decreased; the migration and invasion numbers of H446/AP cells were significantly decreased (P<0.05). LINC00958 targets miR-490-3p, and interference with miR-490-3p expression reverses the inhibitory effect of inhibition of LINC00958 expression on apatatin resistance of H446/AP cells. Therefore, inhibiting the expression of LINC00958 combined with apatinib can inhibit the proliferation, migration and invasion of H446/AP cells, reducing the resistance of small cell lung cancer to apatinib. The mechanism may be related to the expression of miR-490-3p.