Department of Blood Transfusion, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China.
Clinics (Sao Paulo). 2024 Jun 17;79:100407. doi: 10.1016/j.clinsp.2024.100407. eCollection 2024.
NSCLC is one of the most common causes of death. The hypoxia microenvironment contributes to cancer progression. The purpose was to explore the effects and mechanism of melittin on NSCLC cells in the hypoxic microenvironment.
NSCLC cell lines (A549 and H1299) were cultured in normoxia or hypoxia conditions with or without melittin treatment. The viability of the cells was detected via MTT assay and the proliferation ability was evaluated by EdU assay. QRT-PCR was performed to evaluate GLUT1, LDHA, HK2, VEGF and LATS2 mRNA levels. Glucose transport was assessed by the 2-NBDG uptake assay. The angiogenesis was determined by the tubule formation assay. The protein expressions of GLUT1, LDHA, HK2, VEGF, LATS2, YAP, p-YAP and HIF-1α were detected via western blotting assay. The tumor formation assay was conducted to examine the roles of melittin and LATS2 in vivo.
Melittin inhibited hypoxia-induced cell viability, proliferation, glycolysis and angiogenesis as well as suppressed YAP binding to HIF-1α in NSCLC. Melittin inactivated the YAP/HIF-1α pathway via up-regulation of LATS2, ultimately inhibiting cancer progression of NSCLC. Moreover, melittin suppressed tumor growth via up-regulation of LATS2 in vivo.
Melittin inactivated the YAP/HIF-1α pathway via up-regulation of LATS2 to contribute to the development of NSCLC. Therefore, melittin is expected to become a potential prognostic drug for the therapy of NSCLC.
非小细胞肺癌是最常见的死亡原因之一。缺氧微环境促进癌症进展。本研究旨在探讨蜂毒素在缺氧微环境下对非小细胞肺癌细胞的作用及其机制。
在常氧或缺氧条件下，用或不用蜂毒素处理 NSCLC 细胞系（A549 和 H1299）。通过 MTT 法检测细胞活力，通过 EdU 法评估增殖能力。通过 qRT-PCR 评估 GLUT1、LDHA、HK2、VEGF 和 LATS2 mRNA 水平。通过 2-NBDG 摄取实验评估葡萄糖转运。通过管形成实验测定血管生成。通过 Western blot 检测 GLUT1、LDHA、HK2、VEGF、LATS2、YAP、p-YAP 和 HIF-1α 的蛋白表达。通过肿瘤形成实验研究蜂毒素和 LATS2 在体内的作用。
蜂毒素抑制缺氧诱导的 NSCLC 细胞活力、增殖、糖酵解和血管生成，并抑制 YAP 与 HIF-1α 的结合。蜂毒素通过上调 LATS2 使 YAP/HIF-1α 通路失活，最终抑制 NSCLC 的癌症进展。此外，蜂毒素通过上调 LATS2 在体内抑制肿瘤生长。
蜂毒素通过上调 LATS2 使 YAP/HIF-1α 通路失活，从而促进非小细胞肺癌的发展。因此，蜂毒素有望成为治疗非小细胞肺癌的潜在预后药物。
