Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Sichuan, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China.
J Mol Histol. 2024 Dec;55(6):1121-1129. doi: 10.1007/s10735-024-10254-w. Epub 2024 Sep 9.
We aimed to investigate the expression of cancer susceptibility candidate 11 (CASC11) in ovarian cancer (OC) tissues and its role in doxorubicin (Dox) resistance. A total of 98 patients were included as subjects. Reverse transcription-polymerase chain reaction was employed to determine the expressions of CASC11 in OC and para-OC tissues, and in OC cells (A2780, SKOV3, OVCAR3 and A547) and human normal ovarian epithelial cells (IOSE-80) from these patients. OC SKOV3/R cell line with Dox resistance was established and transfected with small interfering (si)-CASC11 to down-regulate CASC11 expression. Based on the constructed nude mouse model of orthotopic transplanted tumor, the growth curves were plotted, and the changes in tumor volume and apoptosis were observed by hematoxylin-eosin staining. OC tissues had a significantly higher mRNA expression of CASC11 than that of para-OC tissues (P < 0.05). A547, OVCAR3, A2780 and SKOV3 cells had significantly higher mRNA expressions of CASC11 than that of IOSE-80 cells (P < 0.05). The transplanted tumor was significantly smaller in volume in the si-CASC11 group than that in the si-normal control (NC) group from the 8th days after transplanted tumor inoculation (P < 0.05). The tumor growth inhibition rate significantly rose in the si-CASC11 group in comparison with that in the si-NC group (P < 0.05). CASC11 has high expression in OC tissues. Knockout of CASC11 weakens the proliferative, invasive and migratory potentials and enhances the apoptotic potential of Dox-resistant OC cells, thereby reversing their Dox resistance.
我们旨在研究抑癌候选基因 11（CASC11）在卵巢癌（OC）组织中的表达及其在多柔比星（Dox）耐药中的作用。共纳入 98 例患者作为研究对象。采用逆转录-聚合酶链反应（RT-PCR）检测 OC 组织和癌旁组织、患者 OC 细胞（A2780、SKOV3、OVCAR3 和 A547）和人正常卵巢上皮细胞（IOSE-80）中 CASC11 的表达。建立 Dox 耐药 OC SKOV3/R 细胞系，并转染小干扰 RNA（siRNA）-CASC11 下调 CASC11 表达。构建裸鼠原位移植瘤模型，绘制生长曲线，HE 染色观察肿瘤体积和凋亡变化。OC 组织中 CASC11 的 mRNA 表达明显高于癌旁组织（P<0.05）。A547、OVCAR3、A2780 和 SKOV3 细胞中 CASC11 的 mRNA 表达明显高于 IOSE-80 细胞（P<0.05）。转染 si-CASC11 后，肿瘤体积从接种后第 8 天起明显小于 si-NC 组（P<0.05）。si-CASC11 组肿瘤生长抑制率明显高于 si-NC 组（P<0.05）。CASC11 在 OC 组织中高表达。敲除 CASC11 可减弱 Dox 耐药 OC 细胞的增殖、侵袭和迁移能力，增强其凋亡能力，从而逆转其 Dox 耐药性。
