Apatinib has anti-tumor effects and induces autophagy in lung cancer cells with high expression of VEGFR-2.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/ijbms.2024.74820.16246
Mingtao Liu, Hui Li
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Abstract

Objectives: This study investigated the inhibitory effect of apatinib on lung cancer cells with high expression of vascular endothelial growth factor-2 (VEGFR-2) and on inducing cellular autophagy and drug resistance.

Materials and methods: The expression of VEGFR-2 was detected using western blotting and RT-PCR. Cell proliferation was measured using the CCK8 and colony formation assays. The cell apoptosis rate was determined using flow cytometry and tunnel assay. Cellular autophagy was detected by measuring the expression of LC3-II using Western blotting and cellular immunofluorescence. The inhibitory effect of apatinib on lung cancer cells and transplanted tumors was observed after treatment with the autophagy inhibitor chloroquine.

Results: Apatinib dose-dependently inhibited the proliferation of H1975 and H446 cells; it induced apoptosis via the PARP and caspase-3 pathways in H1975 and H446 cells and effectively inhibited the growth of transplanted tumors. Apatinib induced autophagy in a dose-dependent manner in H1975 and H446 cells. The inhibitory effect of apatinib on cells and the promotion of apoptosis were significantly enhanced after treatment with chloroquine. Immunohistochemistry showed that combining apatinib with chloroquine could reduce the expression of CD31 and Ki67 and increase the expression of caspase-3.

Conclusion: Apatinib inhibits proliferation and induces apoptosis in H1975 and H1446 lung cancer cells with high VEGFR2 expression and autophagy in H1975 and H446 cells.

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阿帕替尼具有抗肿瘤作用,并能诱导VEGFR-2高表达的肺癌细胞发生自噬。
研究目的本研究探讨了阿帕替尼对高表达血管内皮生长因子-2(VEGFR-2)的肺癌细胞的抑制作用,以及对诱导细胞自噬和耐药性的影响:用 Western 印迹和 RT-PCR 检测血管内皮生长因子-2 的表达。采用 CCK8 和集落形成试验检测细胞增殖。使用流式细胞仪和隧道试验测定细胞凋亡率。使用 Western 印迹法和细胞免疫荧光法测定 LC3-II 的表达,从而检测细胞自噬。在使用自噬抑制剂氯喹治疗后,观察阿帕替尼对肺癌细胞和移植肿瘤的抑制作用:结果:阿帕替尼剂量依赖性地抑制了H1975和H446细胞的增殖;通过PARP和caspase-3途径诱导了H1975和H446细胞的凋亡,并有效抑制了移植肿瘤的生长。阿帕替尼对H1975和H446细胞的自噬诱导具有剂量依赖性。阿帕替尼对细胞的抑制作用和对细胞凋亡的促进作用在氯喹处理后明显增强。免疫组化显示,阿帕替尼与氯喹联用可降低CD31和Ki67的表达,增加caspase-3的表达:阿帕替尼可抑制VEGFR2高表达的H1975和H1446肺癌细胞的增殖并诱导其凋亡,还可抑制H1975和H446细胞的自噬。
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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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