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可生物降解的热敏水凝胶复合材料负载的双药对宫颈癌的高效抑制作用

Efficient inhibition of cervical cancer by dual drugs loaded in biodegradable thermosensitive hydrogel composites.

作者信息

Xu Shan, Du Xiaobo, Feng Gang, Zhang Yu, Li Jie, Lin Binwei, Yang Linglin, Fu Shaozhi, Wu Jingbo

机构信息

Department of Oncology, Mianyang Central Hospital, Mianyang 621000, Sichuan Province, China.

Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China.

出版信息

Oncotarget. 2017 Dec 6;9(1):282-292. doi: 10.18632/oncotarget.22965. eCollection 2018 Jan 2.

Abstract

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 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 ( < 0.05), inhibiting tumor growth ( < 0.05), decreasing expression of CD133 ( < 0.05), CD31 ( < 0.05), and aldehyde dehydrogenase 1 (ALDH1) ( > 0.05), inducing G1 phase arrest ( < 0.05), increasing the apoptosis rate ( < 0.05), and in expressing ATM and γ-H2AX ( < 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.

摘要

背景与目的

我们旨在探究含顺铂(DDP)的热敏水凝胶(PEG - PCL - PEG,或PECE)与载紫杉醇(PTX)的MPEG - PCL聚合物胶束(称为PDMP)联合使用对人宫颈癌(HeLa)细胞的抗肿瘤作用及机制。在我们之前的研究中,我们发现PDMP治疗肺癌对肺癌患者可能具有潜在疗效。

结果

与其他治疗方法相比,PDMP在延长生存时间(<0.05)、抑制肿瘤生长(<0.05)、降低CD133(<0.05)、CD31(<0.05)和醛脱氢酶1(ALDH1)的表达(>0.05)、诱导G1期阻滞(<0.05)、提高凋亡率(<0.05)以及表达共济失调毛细血管扩张突变蛋白(ATM)和γ - H2AX(<0.05)方面最为有效。

结论

在宫颈癌治疗方面,PDMP被视为一种有前景的抗肿瘤反应物。

方法

我们使用异种移植宫颈癌模型来验证PDMP的抗肿瘤活性并探究其作用机制。给小鼠瘤内注射生理盐水、PECE、PTX + DDP或PDMP。治疗两天后,每组处死三只小鼠并收集肿瘤组织。通过免疫组织化学测定组蛋白H2AX磷酸化(γ - H2AX)水平,通过蛋白质印迹分析测量共济失调毛细血管扩张突变蛋白(ATM)水平。此外,在10天的治疗后每组将处死三只小鼠,并且通过流式细胞术和免疫组织化学分析收获肿瘤。我们将使用其余的小鼠来分析肿瘤生长和存活情况。其余小鼠用于分析肿瘤生长和存活情况。

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