海葵苷B4和粉防己碱对奥沙利铂耐药人结肠癌细胞的逆转耐药作用及机制

Q4 Medicine

中国癌症杂志 Pub Date : 2015-05-08 DOI:10.3969/J.ISSN.1007-3969.2015.01.007

L. Min, Fang Mingzhi

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引用次数: 3

摘要

背景与目的:奥沙利铂(Oxaliplatin, L-OHP)是结直肠癌最常用的化疗药物之一，L-OHP耐药在结直肠癌治疗中十分常见。本研究旨在探讨anemoside B4(AB4)和粉防己碱(Tet)对L-OHP耐药人结肠癌细胞株Lo Vo/L-OHP的逆转作用，并阐明其分子机制。方法:以不同浓度的AB4和Tet作用于Lo Vo/L-OHP细胞48 h，获得无毒剂量。采用MTT法测定药物敏感性。处理后检测细胞周期和细胞凋亡情况。RT-PCR检测P-gp m RNA、z - DHHC9 m RNA和SMAD4 m RNA的表达。Western blot检测P-gp、z DHHC9和SMAD4蛋白的表达。结果:经0.71 μg/m L AB4和0.45 μg/m L Tet(无毒剂量)处理后，Lo Vo/L- ohp对L- ohp的IC50分别为(112.5±23.6)μg/m L和(62.8±21.4)μg/m L(P0.05)和(58.9±26.3)μ L(P0.05)。细胞周期实验显示G1期细胞数量减少，S期细胞数量增加，但差异无统计学意义(P0.05)。细胞凋亡实验显示，无毒剂量的AB4和Tet处理后，细胞凋亡率升高，但无统计学意义(P0.05)。RT-PCR实验显示，与Lo Vo细胞相比，Lo Vo/L-OHP细胞中P-gp m RNA和z - DHHC9 m RNA的表达增加(P0.05)， SMAD4 m RNA的表达减少(P0.05)，而无毒剂量AB4处理后，Lo Vo/L-OHP细胞中P-gp m RNA的表达减少(P0.05)。Western blot实验显示，AB4处理后，Lo Vo/L-OHP细胞中P-gp蛋白含量降低(P0.05)，与PCR结果一致。Tet作用后，Lo Vo/L-OHP细胞中z DHHC9蛋白表达降低(P0.05)。结论:AB4和Tet对Lo Vo/L-OHP细胞的L-OHP耐药有一定的逆转作用。抗性逆转作用的分子机制与P-gp对AB4的下调和z DHHC9对Tet的下调有关。

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Resistance reverse effect of anemoside B4 and tetrandrine on oxaliplatin-resistant human colon cancer cells and the mechanism

Background and purpose: Oxaliplatin(L-OHP) is one of the most commonly used chemotherapy drugs in colorectal cancer and L-OHP-resistance is very common in colorectal cancer therapy. This research was to discuss the reversal effect in L-OHP-resistant human colon cancer cell line Lo Vo/L-OHP by anemoside B4(AB4) and tetrandrine(Tet) and to clarify their molecular mechanism. Methods: Lo Vo/L-OHP cells were treated for 48 h by AB4 and Tet at different concentrations to get non-toxic dose. Drug sensitivity was measured by MTT. After the treatment, the cell cycle and apoptosis of the cells were detected. Expression of P-gp m RNA, z DHHC9 m RNA and SMAD4 m RNA were detected by RT-PCR. Expression of P-gp, z DHHC9 and SMAD4 protein were detected by Western blot. Results: The IC50 of Lo Vo/L-OHP for L-OHP was(112.5±23.6) μg/m L, and the IC50 decreased to(62.8±21.4) μg/m L(P0.05) and(58.9±26.3) μg/m L(P0.05) after the treatment with 0.71 μg/m L AB4 and 0.45 μg/m L Tet(non-toxic dose) separately. The cell cycle experiment showed that the cells in G1 stage decreased and in S stage increased but with no statistical significance(P0.05). The cell apoptosis experiment showed that the apoptotic rate increased after the treatment with AB4 and Tet with non-toxic dose but with no statistical significance(P0.05). The RT-PCR experiment showed that the expressions of P-gp m RNA and z DHHC9 m RNA were increased and SMAD4 m RNA was decreased in Lo Vo/L-OHP cells compared with in Lo Vo cells(P0.05), while it was found that P-gp m RNA in Lo Vo/L-OHP cells was decreased after the treatment with AB4 at non-toxic dose(P0.05). Western blot experiment showed the protein of P-gp in Lo Vo/L-OHP cells was decreased after treatment with AB4(P0.05), which was accordant to the PCR result. The expression of z DHHC9 protein in Lo Vo/L-OHP cells was decreased in Lo Vo/L-OHP cells after treatment with Tet(P0.05). Conclusion: AB4 and Tet have some reversal effect on resistant to L-OHP in Lo Vo/L-OHP cells. The molecular mechanism of the resistance reverse effect was related to down-regulation of P-gp for AB4 and down-regulation of z DHHC9 for Tet.

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来源期刊

中国癌症杂志 Medicine-Oncology

CiteScore

0.50

自引率

0.00%

发文量

5398

期刊介绍： The journal of China Oncology (ISSN 1007-3639, CN 31-1727/R) started in 1991, is a peer-reviewed monthly publication, integrating scientific information from global sources for all oncologic specialties. It is an open access monthly published journal in Chinese and English. The competent authorities of China Oncology is the Ministry of Education of the People’s Republic of China. China Oncology is hosted by one of the most prestigious comprehensive cancer centers, the Fudan University Shanghai Cancer Center. Database Index At present, China Oncology is indexed in the following most powerful database: SCOPUS, DOAJ, Chemical Abstracts (CAS), EMBASE, EBSCO, Japan Science and Technology Database (JST), Index of Copernicus International (ICI) and Western Pacific Region Index Medicus (WPRIM), Ulrich's Periodical Directory, Chinese Science Citation Database (CSCD), A Guide to the Core Journal of China, Chinese Scientific and Technical Papers and Citations Database (CSTPCD), Chinese Academic Journal Comprehensive Evaluation Database (CAJCED), Chinese Medical Current Content (CMCC), Chinese Medical Citation Index (CMCI),Chinese Biological Abstracts (CBA), GoOA,COAJ, Level A of Fudan University degree and Graduate Education Domestic Journals Guideline, Research Center for Chinese Science Evaluation (RCCSE), World Journal Clout Index (WJCI) Report of Scientific and Technological Periodicals (2023). Besides, China Oncology continuously acquired Certificate of Outstanding S&T Journals of China (F5000) since 2017.