Ardalan Moghadam Al Fatemeh, Forghanifard Mohammad Mahdi, Zarrinpour Vajiheh
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
Med Oncol. 2025 Jan 14;42(2):45. doi: 10.1007/s12032-024-02590-4.
5-FU is a widely used chemotherapy drug for esophageal carcinomas, but therapy failure has been observed in 5-FU-resistant patients. Overcoming this resistance is a significant challenge in cancer treatment, requiring identifying and targeting important resistance mechanisms. PYGO2 expression is crucial in developing resistance to various chemotherapy drugs. In this study, we aimed to investigate the impact of PYGO2 overexpression on the sensitivity of YM-1 and KYSE-30 esophageal carcinoma cells against 5-FU. To do this, we compared cell viability, cell cycle arrest, apoptosis rate, and mRNA expressions of various apoptosis-related genes between pcDNA3-PYGO2 transfected and untransfected KYSE-30 and YM-1 esophageal carcinoma cells following treatment with 5-FU. We showed that PYGO2 expression reduces 5-FU sensitivity in YM-1 and KYSE-30 cells. PYGO2-overexpressing cells treated with 5-FU have exhibited a noteworthy reduction in both early and late apoptotic cells compared to controls. Furthermore, a significant decrease in the Bax/Bcl2 ratio and P53 gene expression was observed. 5-FU induces G2/M cell cycle arrest in YM-1 and KYSE-30 cells. However, PYGO2 overexpression impeded G2/M cell cycle arrest in 5-FU-treated cells, thereby suppressing the toxicity of 5-FU. PYGO2 may mediate its apoptotic effect by regulating cell cycle regulatory proteins, specifically cyclin D1 and p21. These results highlight PYGO2's capacity to alter how esophageal cancer cells respond to 5-FU therapy, emphasizing its importance as a potential focal point for treatment strategies.
5-氟尿嘧啶是一种广泛用于治疗食管癌的化疗药物，但在对5-氟尿嘧啶耐药的患者中已观察到治疗失败。克服这种耐药性是癌症治疗中的一项重大挑战，需要识别并靶向重要的耐药机制。PYGO2的表达在对各种化疗药物产生耐药性的过程中至关重要。在本研究中，我们旨在探讨PYGO2过表达对YM-1和KYSE-30食管癌细胞对5-氟尿嘧啶敏感性的影响。为此，我们比较了用5-氟尿嘧啶处理后，转染pcDNA3-PYGO2的和未转染的KYSE-30及YM-1食管癌细胞之间的细胞活力、细胞周期阻滞、凋亡率以及各种凋亡相关基因的mRNA表达。我们发现，PYGO2的表达降低了YM-1和KYSE-30细胞对5-氟尿嘧啶的敏感性。与对照组相比，用5-氟尿嘧啶处理的PYGO2过表达细胞在早期和晚期凋亡细胞方面均有显著减少。此外，观察到Bax/Bcl2比值和P53基因表达显著降低。5-氟尿嘧啶可诱导YM-1和KYSE-30细胞发生G2/M期细胞周期阻滞。然而，PYGO2过表达阻碍了5-氟尿嘧啶处理细胞中的G2/M期细胞周期阻滞，从而抑制了5-氟尿嘧啶的毒性。PYGO2可能通过调节细胞周期调节蛋白，特别是细胞周期蛋白D1和p21来介导其凋亡作用。这些结果突出了PYGO2改变食管癌细胞对5-氟尿嘧啶治疗反应的能力，强调了其作为治疗策略潜在重点的重要性。
