目的：探讨维生素C（vitamin C，VC）逆转口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC或口腔鳞癌）顺铂（cis‐platin，DDP）耐药的作用及其机制。方法：选用体外培养的人口腔鳞癌CAL27细胞，用浓度梯度递增法筛选出耐DDP的CAL27/DDP细胞株，用平板克隆形成实验、CCK-8、划痕愈合实验、Annexin V-FITC/PI染色流式细胞术分别检测单独应用DDP以及联合VC 对 CAL27/DDP 细胞克隆形成、细胞增殖、迁移和凋亡的影响，Wester blotting 分别检测 CAL27、CAL27/DDP 和 VC 处理后CAL27/DDP 细胞中 P-gp 蛋白的表达变化。结果：DDP 对 CAL27/DDP 细胞的 IC50比 CAL27 细胞显著上升（P<0.05），CAL27/DDP细胞对DDP耐药；联合VC后，DDP对CAL27/DDP细胞的IC50比DDP单用时显著降低（P<0.05）。DDP联合VC能显著抑制CAL27/DDP细胞的迁移能力（P<0.01），同时提高细胞的凋亡率（P<0.01）。CAL27/DDP细胞中P-gp蛋白表达水平相对CAL27细胞升高（P<0.05），在VC干预后其表达水平下降（P<0.05）。结论：VC可逆转口腔鳞癌细胞DDP耐药，此种逆转作用是通过抑制P-gp蛋白表达实现的

Objective: To study the effects of vitamin C (VC) on reversing cisplatin (DDP) resistance in oral squamous cell carcinoma (OSCC) and the mechanism. Methods: Human OSCC CAL27 cells were cultured in vitro and DDP-resistant CAL27 cell line (CAL27/DDP) was screened by increasing concentration gradient method. Plate clone formation assay, CCK-8, Wound healing assay, Annexin V-FITC/PI staining flow cytometry were used to determine the effects of DDP alone or in combination with VC on colony formation,proliferation, migration and apoptosis of CAL27/DDP cells. Western blotting was used to detect the expression level of P-gp protein in CAL27 cells, CAL27/DDP cells and VC treated CAL27/DDP cells. Results: The inhibition concentration (IC50) of DDP increased significantly in CAL27/DDP cells as compared with that in CAL27 cells (P<0.05), indicating CAL27/DDP was DDP-resistant. After the combination with VC, the IC50 of DDP on CAL27/DDP cells was significantly reduced compared with that of DDP alone (P<0.05).DDP combined with VC significantly inhibited the migration of CAL27/DDP cells (P<0.01), and promoted the apoptosis rate (P<0.01).The expression level of P-gp protein in CAL27/DDP cells was increased compared with that in CAL27 cells (P<0.05), but decreased after VC intervention (P<0.05). Conclusion: VC can reverse DDP-resistance in OSCC cells by inhibiting P-gp protein expression.

上海市自然科学基金资助项目（No. 17ZR1439200）