baohuoside-i and Ovarian-Neoplasms

Since chemotherapy's therapeutic impact is diminished by drug resistance, treating ovarian cancer is notably challenging. Thereafter, it is critical to develop cutting-edge approaches to treating ovarian cancer. Baohuoside I (derived from Herba Epimedii) is reported to have antitumor properties in various malignancies. It is unknown, however, what role Baohuoside I plays in cisplatin (DDP)-resistant ovarian cancer cells. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), colony formation, and flow cytometry assay were used to investigate the impact of Baohuoside I on ovarian cancer A2780 cells and DDP-resistant A2780 (A2780/DDP) cells. The level of microtubule associated protein 1 light chain 3 (LC3) was determined using immunofluorescence staining. Utilizing the mRFP-GFP-LC3B tandem fluorescent probe allowed us to analyse the autophagy flux. Analysis of mRNA and protein level was performed using RT-qPCR and Western blot analysis, respectively. The interaction between hypoxia inducible factor 1 subunit alpha (HIF-1α) and autophagy related 5 (ATG5) promoter was investigated by dual luciferase and ChIP assay. Additionally, evaluation of Baohuoside I's role in ovarian cancer was performed using a nude mouse xenograft model. Baohuoside I decreased the viability and proliferation and triggered the apoptosis of both A2780 and A2780/DDP cells in a concentration-dependent manner. Baohuoside I also increased the sensitivity of A2780/DDP cells to DDP. Concurrently, HIF-1α could promote A2780/DDP cells resistance to DDP. In addition, HIF-1α could induce the autophagy of A2780/DDP cells through transcriptionally activating ATG5, and Baohuoside I imporved the chemosensitivity of A2780/DDP cells to DDP by downregulating HIF-1α. Moreover, Baohuoside I could inhibit the chemoresistance to DDP in ovarian cancer in vivo. Baohuoside I sensitizes ovarian cancer cells to DDP by suppressing autophagy via downregulating the HIF-1α/ATG5 axis. Consequently, Baohuoside I might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of drug treatment for ovarian cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Autophagy-Related Protein 5; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Female; Humans; Mice; Ovarian Neoplasms

Ovarian cancer is one of the three major gynecological malignancies. It has been reported that Icariside II was able to block the occurrence and development of ovarian cancer. However, the detailed mechanism by which Icariside II regulates the development of ovarian cancer is widely unknown. EdU staining and transwell assays were applied to detect the proliferation, migration, and invasion of ovarian cancer cells. Next, the relationship between miR-144-3p and IGF2R was verified by the dual-luciferase reporter assay. Moreover, in vivo animal model was constructed to verify the effect of Icariside II on the development of ovarian cancer. Icariside II notably inhibited the proliferation, migration, and invasion and induced the apoptosis of ovarian cancer cells. Additionally, Icariside II markedly increased the level of miR-144-3p in ovarian cancer cells. Moreover, IGF2R was targeted by miR-144-3p directly. Icariside II significantly decreased the expression of IGF2R and the phosphorylation level of AKT and mTOR in ovarian cancer cells, which were partially reversed by miR-144-3p inhibitor. Meanwhile, Icariside II remarkably promoted the autophagy of ovarian cancer cells, as confirmed by the increased expression of Beclin-1 and ATG-5 and decreased expression of p62; however, co-treatment with miR-144-3p inhibitor notably decreased autophagy. Furthermore, the result of animal study suggested Icariside II notably inhibited ovarian tumor growth as well. Collectively, Icariside II could suppress the tumorigenesis and development of ovarian cancer by promoting autophagy via miR-144-3p/IGF2R axis. These results may be beneficial for future studies on the use of Icariside II to treat ovarian cancer.

Topics: Animals; Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Flavonoids; Humans; MicroRNAs; Ovarian Neoplasms