含奥沙利铂 (OXA) 的方案被用作结直肠癌 (CRC) 的一线化疗。然而，OXA 耐药仍然是 CRC 治疗的主要挑战。适应缺氧的CRC细胞可能会产生OXA耐药性，其潜在的分子机制仍需要进一步研究。在当前的研究中，比较了两种CRC细胞系HCT116 (TP53WT)和HT29 (TP53MT)在常氧和低氧条件下的OXA药物敏感性。结果发现，在常氧条件下，HCT116细胞表现出明显高于HT29细胞的OXA敏感性。然而，两种细胞系在缺氧条件下均表现出显着的 OXA 抗性。还发现，HCT116 细胞中 OXA 和缺氧处理后 P53 水平升高，但 HT29 细胞中 P53 水平没有升高。值得注意的是，敲低 P53WT 会降低 HCT116 细胞的常氧 OXA 敏感性，但会增加缺氧 OXA 敏感性，而这在 HT29 细胞中并不存在。分子分析表明，P53WT 在 OXA 治疗中激活 microRNA (miR)-26a 和 miR-34a，在缺氧治疗中激活 miR-23a。细胞增殖实验表明，高水平的 miR-23a 会降低 HCT116 细胞中的 OXA 敏感性，而高水平的 miR-26a 或 miR-34a 会增加 HCT116 细胞中的 OXA 敏感性。此外，研究还表明，miR-26a、miR-34a 和 miR-23a 通过调节 MCL-1、EZH2、BCL-2、SMAD 4 和 STAT3 影响细胞凋亡。总而言之，目前的研究结果揭示了 P53 在调节细胞化疗敏感性方面的双重功能，并强调了 P53-miR 相互作用在常氧和缺氧条件下 CRC 细胞对 OXA 化疗反应中的作用。

Oxaliplatin (OXA)‑containing regimens are used as first‑line chemotherapy in colorectal cancer (CRC). However, OXA resistance remains a major challenge in CRC treatment. CRC cells that adapt to hypoxia can potentially develop OXA resistance, and the underlying molecular mechanisms still need to be further investigated. In the current study, the OXA drug sensitivity of two CRC cell lines, HCT116 (TP53WT) and HT29 (TP53MT), was compared under both normoxic and hypoxic conditions. It was found that under normoxic condition, HCT116 cells showed significantly higher OXA sensitivity than HT29 cells. However, both cell lines showed remarkable OXA resistance under hypoxic conditions. It was also revealed that P53 levels were increased after OXA and hypoxia treatment in HCT116 cells but not in HT29 cells. Notably, knocking down P53WT decreased normoxic but increased hypoxic OXA sensitivity in HCT116 cells, which did not exist in HT29 cells. Molecular analysis indicated that P53WT activated microRNA (miR)‑26a and miR‑34a in OXA treatment and activated miR‑23a in hypoxia treatment. Cell proliferation experiments indicated that a high level of miR‑23a decreased OXA sensitivity and that a high level of miR‑26a or miR‑34a increased OXA sensitivity in HCT116 cells. Additionally, it was demonstrated that miR‑26a, miR‑34a and miR‑23a affect cell apoptosis through regulation of MCL‑1, EZH2, BCL‑2, SMAD 4 and STAT3. Taken together, the present findings revealed the dual function of P53 in regulating cellular chemo‑sensitivity and highlighted the role of P53‑miR interactions in the response of CRC cells to OXA chemotherapy under normoxic and hypoxic conditions.