Squamous cell carcinoma (SCC) is nonmelanoma skin cancer, which is very common in patients having T‐cell immunosuppressant drugs. Anticancerous agents such as cytokines showed effective response on SCC. Human interferon‐gamma (hIFN‐γ), a type II cytokines, are having potent antiproliferative and immunomodulatory effects. In the current study, the fed‐batch cultivation of recombinant Pichia pastoris was carried out, and its effect on cell biomass production, recombinant human interferon‐gamma (rhIFN‐γ) production, and the overflow metabolites was estimated. P. pastoris GS115 strain coexpressed with 6‐phosphogluconolactonase (SOL3) and ribulose‐phosphate 3‐epimerase (RPE1) gene (GS115/rhIFN‐γ/SR) resulted in 60 mg L⁻¹ of rhIFN‐γ production, which was twofold higher as compared with the production from GS115/rhIFN‐γ strain. The antiproliferative potential of rhIFN‐γ was examined on the human squamous carcinoma (A431) cell lines. Cells treated with 80 ng mL⁻¹ of rhIFN‐γ exhibited 50% growth inhibition by enhancing the production of intracellular reactive oxygen species levels and disrupting membrane integrity. Our findings highlight a state of art process development strategy for the high‐level production of rhIFN‐γ and its potential application as a therapeutic drug in SCC therapy.

中文翻译：

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基于葡萄糖-甲醇的分批补料发酵，用于生产重组人干扰素γ（rhIFN-γ）并评估其抗肿瘤潜力。

鳞状细胞癌（SCC）是非黑色素瘤皮肤癌，在患有T细胞免疫抑制剂药物的患者中非常常见。抗癌剂（例如细胞因子）对SCC表现出有效的反应。人类干扰素-γ（hIFN-γ）是一种II型细胞因子，具有强大的抗增殖和免疫调节作用。在本研究中，进行了巴斯德毕赤酵母的分批分批培养，并评估了其对细胞生物量产生，重组人干扰素-γ（rhIFN-γ）产生和溢流代谢产物的影响。与6-磷酸葡萄糖酸内酯酶（SOL3）和核糖磷酸3-表异构酶（RPE1）基因（GS115 /rhIFN-γ/ SR）共表达的巴斯德毕赤酵母GS115菌株产生60 mg L ^-1rhIFN-γ的产量，比GS115 /rhIFN-γ菌株的产量高两倍。在人鳞癌（A431）细胞系中检测了rhIFN-γ的抗增殖潜力。用80 ng mL ^-1的rhIFN-γ处理的细胞通过增强细胞内活性氧的产生并破坏膜的完整性，表现出50％的生长抑制作用。我们的发现突出了高水平生产rhIFN-γ及其在SCC治疗中作为治疗药物的潜在应用的最新工艺开发策略。