Marzan Mahfuza, Nowshin Oishee Nuzhat, Olatunji Abigail Oluwafisayo, Hasib Shourav Abiral, Noor Radwan Ebna, Astalos Aaron Joshua, Leahy James W, Acevedo-Duncan Mildred
Department of Chemistry, University of South Florida, 4202 E Fowler Ave, CHE 205, Tampa, FL 33620, USA.
Int J Mol Sci. 2025 Mar 26;26(7):3035. doi: 10.3390/ijms26073035.
Ovarian cancer is the most lethal gynecological cancer, with a 5-year survival rate of approximately 50%. Mutation in the p53 gene and overexpression of the atypical protein kinase C iota (PKC-ι) are two phenomena widely manifested in ovarian cancer. This study investigated the role of PKC-ι-specific inhibitor ICA-1S and proteasome inhibitor MG-132 in ovarian cancer cell lines. To discern the result, cell proliferation assays, cytotoxicity assays, Western blotting, immunofluorescence, flow cytometry, small interfering RNA, and co-immunoprecipitation techniques were applied. ICA-1S and MG-132 were found to inhibit the proliferation of ovarian cancer cell lines significantly. ICA-1S reduced the level of oncogenic PKC-ι as expected. In addition, ICA-1S and MG-132 both were able to decrease the level of mutated p53 in the ES-2 cell line through separate pathways. On the contrary, MG-132 increased the level of wild-type p53 in the HEY-T30 cell line by inhibiting proteasomal degradation. MG-132 also induced apoptosis and autophagy in the ovarian cancer cell lines. We concluded that ICA-1S alone or in combination with MG-132 could be a potential treatment for mutated p53-containing and PKC-ι-overexpressing ovarian cancers.
卵巢癌是最致命的妇科癌症，5年生存率约为50%。p53基因的突变和非典型蛋白激酶Cι（PKC-ι）的过表达是卵巢癌中广泛表现的两种现象。本研究调查了PKC-ι特异性抑制剂ICA-1S和蛋白酶体抑制剂MG-132在卵巢癌细胞系中的作用。为了辨别结果，应用了细胞增殖试验、细胞毒性试验、蛋白质印迹法、免疫荧光法、流式细胞术、小干扰RNA和免疫共沉淀技术。发现ICA-1S和MG-132能显著抑制卵巢癌细胞系的增殖。正如预期的那样，ICA-1S降低了致癌性PKC-ι的水平。此外，ICA-1S和MG-132都能够通过不同途径降低ES-2细胞系中突变型p53的水平。相反，MG-132通过抑制蛋白酶体降解增加了HEY-T30细胞系中野生型p53的水平。MG-132还诱导卵巢癌细胞系发生凋亡和自噬。我们得出结论，ICA-1S单独使用或与MG-132联合使用可能是治疗含突变型p53和PKC-ι过表达的卵巢癌的一种潜在方法。
