Efficient inhibition of cervical cancer by dual drugs loaded in biodegradable thermosensitive hydrogel composites
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Shan Xu1, Xiaobo Du1, Gang Feng1, Yu Zhang1, Jie Li1, Binwei Lin1, Linglin Yang2, Shaozhi Fu2 and Jingbo Wu2
1Department of Oncology, Mianyang Central Hospital, Mianyang 621000, Sichuan Province, China
2Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
Jingbo Wu, email: [email protected]
Shaozhi Fu, email: [email protected]
Shan Xu, email: [email protected]
Keywords: cervical cancer; cisplatin; paclitaxel; thermosensitive hydrogel; micelles
Received: August 24, 2017 Accepted: November 09, 2017 Published: December 06, 2017
Background and Purpose: We aimed to explore the anti-tumor effect and mechanism of the combination of cisplatin (DDP)-containing thermosensitive hydrogel (PEG-PCL-PEG, or PECE) and paclitaxel (PTX)-loaded MPEG-PCL polymeric micelles called PDMP on human cervical carcinoma (HeLa) cell. In our previous studies, we found that PDMP in situ treatment of lung cancer will be liable to have potential in Lung cancer patients.
Results: Compared with other treatments, PDMP was most effective in prolonging survival time (P < 0.05), inhibiting tumor growth (P < 0.05), decreasing expression of CD133 (P < 0.05), CD31 (P < 0.05), and aldehyde dehydrogenase 1 (ALDH1) (P > 0.05), inducing G1 phase arrest (P < 0.05), increasing the apoptosis rate (P < 0.05), and in expressing ATM and γ-H2AX (P < 0.05).
Conclusions: PDMP is regarded as a promising anti-tumor reactant, when it comes to the treatment of cervical carcinoma.
Methods: we used a xenograft cervical cancer model to verify the anti-tumor activity of PDMP and to explore its mechanism of action. Mice were intratumorally administered with NS, PECE, PTX+DDP or PDMP. After two days of treatment, three mice per group were sacrificed and tumor tissue was harvested. Levels of histone H2AX phosphorylation (γ-H2AX) were determined by immunohistochemistry and ataxia telangiectasia mutated(ATM) protein levels were measured by western blot analysis. In addition, it would sacrifice each of group of three mice through 10 days’ treatment, what’s more, it would harvest tumor by virtue of flow cytometry and immunohistochemical analysis. It would like to use there maining mice to analyze tumor growth and survival. The remaining mice were analyzed for tumor growth and survival.
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