Antitumor effect of thermosensitive hydrogel co-loading paclitaxel and cisplatin on cervical cancer / 肿瘤

ABSTRACT

Objective: To develop a hydrogel-based drug delivery system coloading cisplatin (DDP) and paclitaxel (PTX), polyethylene glycolpolycaprolactone- polyethylene glycol (PECE)/DDP+methoxypolyethylene glycols-polycaprolactone (MPEG-PCL)/PTX (or PDMP in short), and to explore the therapeutic efficacy of PDMP hydrogel on cervical cancer in animal model and the possible mechanism. Methods: MPEG-PCL/PTX micelles were successfully synthesized by solid dispersion method. Then the PDMP gel-drug system was successfully developed after mixing MPEG-PCL/PTX with PECE hydrogel and DDP solution, and the physical and chemical properties of PDMP were verified by high performance liquid chromatography, rheometer and laser particle size analysis, respectively. The cervical cancer model of HeLa cells in nude mice was established and randomly divided into four groups control group (0.9% NaCl solution), simple vector group (PECE+MPEG-PCL), free drug group (PTX+DDP) and PDMP gel drug group (12 mice in each group). The tumor-beared mice in the different groups were intratumorally administered with different drugs, then the tumor growth was observed. Half of the mice in each group (n = 6) were sacrificed after 10 days of treatment, and tumor tissues were harvested for immunohistochemistry and flow cytometry in order to evaluate Ki-67 expression, cell cycle distribution and apoptosis. The remaining tumor-beared mice in each group (n = 6) were cultured, and the survival time was observed. Results: PDMP gel drug system was successfully prepared. As compared with the other groups, PDMP inhibited tumor growth in nude mice and improved the survival time of tumor-bearing nude mice (all P<0.05). After PDMP treatment, the positive expression rate of Ki-67 in xenograft tumors was significantly reduced as compared with the other groups (all P<0.05), suggesting that the proliferation activity of tumor cells was decreased. PDMP caused the cell block at G1 phase, and increased the apoptosis rate as compared with the other groups (all P<0.05). Conclusion: PDMP may be a promising intratumoral drug delivery system to enhance antitumor efficacy for the treatment of cervical cancer in situ.