The role of a drug-loaded poly (lactic co-glycolic acid) (PLGA) copolymer stent in the treatment of ovarian cancer

Yanqing Wang, et al, Xiaoyin Qiao, Xiao Yang, et al.

Abstract


Objectives: Cisplatin (CDDP) is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer. However, adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy tosolve this problem.

Methods: In this study, 3D printing technology was used to prepare a CDDP-poly (lactic-co-glycolic acid) (CDDP-PLGA) polymercompound stent, and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.

Results: The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneoustumors in nude mice, whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection. Compared withthe control group, CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein (P < 0.01; P < 0.01) and decreasedvascular endothelial growth factor mRNA (P < 0.05) and protein levels (P < 0.01), however, CDDP-PLGA significantly decreased themRNA and protein levels of p-glycoprotein (P < 0.01; P < 0.01) and vascular endothelial growth factor (P < 0.01; P < 0.01), which areassociated with chemoresistance, in subcutaneous tumor tissue. Immunohistochemistry assay results revealed that, in the CDDP-PLGAgroup, the staining of the proliferation-related genes Ki67 and PCNA were lightly, and the apoptosis-related gene caspase-3 stained deeply.

Conclusions: PLGA biomaterials loaded with CDDP, as compared with the same amount of free CDDP, showed good efficacy interms of cytotoxicity, as evidenced by changes in apoptosis. Continuous local CDDP release can decrease the systemic side effects ofthis drug and the occurrence of drug resistance and angiogenesis, and improve the therapeutic effect. This new approach may be aneffective strategy for the local treatment of epithelial ovarian cancer.

Cite this article as: Wang Y, Qiao X, Yang X, Yuan M, Xian S, Zhang L, et al. The roleof a drug-loaded poly (lactic co-glycolic acid) (PLGA) copolymer stent in thetreatment of ovarian cancer. Cancer Biol Med. 2020; 17: 237-250. doi: 10.20892/j.issn.2095-3941.2019.0169


Keywords


3D printing; drug-loaded stent; local treatment; cisplatin; ovarian cancer

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