Liu Xia, Zhang Jun, Xia Lianping, Su Yuting, Chen Xiaoying, Wang Cong, Ouyang Yiqiang, Yin Fuqiang
Key Laboratory of Longevity and Ageing-Related Disease of Chinese Ministry of Education, Centre for Translational Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, 530021, China.
Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, China.
Sci Rep. 2025 Jul 1;15(1):20399. doi: 10.1038/s41598-025-07055-w.
Ovarian cancer is the most lethal tumor in female reproductive system, which seriously threatens the life and health of women. Our previous study found that LAMC3 was down-regulated in ovarian cancer tissues and correlated with ovarian cancer resistance. However, the effects of LAMC3 interference on drug resistance in carboplatin-resistant ovarian cancer cells remain unknown. In the present study, the effects of LAMC3 interference on drug resistance, cell proliferation, cycle, apoptosis, and ultrastructure of carboplatin-resistant ovarian cancer cells were examined. The results showed that LAMC3 interference lowered drug resistance of carboplatin-resistant ovarian cancer cells. The cell proliferation was inhibited and cell apoptosis was promoted in carboplatin-resistant ovarian cancer cells with LAMC3 interference. Besides, LAMC3 interference arrested cell cycle and affected cell ultrastructure of carboplatin-resistant ovarian cancer cells. Furthermore, transcriptome sequencing and WB verification results revealed cell cycle, autophagy, ferroptosis, lysosome related key pathway proteins may be involved in LAMC3 interference regulating drug resistance of carboplatin-resistant ovarian cancer cells. This study indicated LAMC3 interference reduced drug resistance of carboplatin-resistant ovarian cancer cells principal by affecting cell cycle, autophagy, ferroptosis, and lysosome. The present study provides a potential target for clinical treatment of drug resistance in ovarian cancer.
卵巢癌是女性生殖系统中最致命的肿瘤，严重威胁着女性的生命健康。我们之前的研究发现，LAMC3在卵巢癌组织中表达下调，且与卵巢癌耐药相关。然而，LAMC3干扰对耐卡铂卵巢癌细胞耐药性的影响尚不清楚。在本研究中，我们检测了LAMC3干扰对耐卡铂卵巢癌细胞的耐药性、细胞增殖、周期、凋亡及超微结构的影响。结果显示，LAMC3干扰降低了耐卡铂卵巢癌细胞的耐药性。LAMC3干扰的耐卡铂卵巢癌细胞的增殖受到抑制，细胞凋亡增加。此外，LAMC3干扰使耐卡铂卵巢癌细胞的细胞周期停滞，并影响其细胞超微结构。此外，转录组测序和WB验证结果表明，细胞周期、自噬、铁死亡、溶酶体相关关键通路蛋白可能参与LAMC3干扰调控耐卡铂卵巢癌细胞的耐药性。本研究表明，LAMC3干扰主要通过影响细胞周期、自噬、铁死亡和溶酶体来降低耐卡铂卵巢癌细胞的耐药性。本研究为卵巢癌耐药的临床治疗提供了一个潜在靶点。
