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紫花苜蓿提取物通过诱导细胞凋亡和调节BAX/BCL-2/CASP3表达增强吉西他滨对PANC-1细胞的抗癌疗效。

Medicago sativa Extracts Enhance the Anticancer Efficacy of GEM in PANC-1 Cells through Apoptosis Induction and BAX/BCL-2/CASP3 Expression Modulation.

作者信息

Jamshidi Nazanin, Jamshidi Negar, Zaman Mohammad, Chehrehsaz Mahta, Roshanfarzad Farnaz, Chaleshi Vahid, Asadzadeh Aghdaei Hamid

机构信息

Kimia Andisheh Teb, Medical and Molecular Laboratory Research Co., Tehran, Iran.

Department of Genetics, Islamic Azad University Tehran Medical Branch, Tehran, Iran.

出版信息

Asian Pac J Cancer Prev. 2025 May 1;26(5):1689-1700. doi: 10.31557/APJCP.2025.26.5.1689.

DOI:10.31557/APJCP.2025.26.5.1689
PMID:40439381
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12290208/
Abstract

INTRODUCTION

Pancreatic cancer (PC) has a poor prognosis and limited response to therapies. Combinatorial approaches, such as natural product-based therapies, can enhance anticancer efficacy while minimizing side effects. This study evaluated M. sativa's anticancer properties and its potential as adjunctive therapy with Gemcitabine (GEM) to sensitize PANC-1 cells to chemotherapy.

METHODS

The antioxidant activity (AA) and total phenolic content (TPC) of M. sativa extracts (Methanol, Ethyl acetate, and water) were assessed using the DPPH radical scavenging assay. Cytotoxic effects on PANC1 and HUVEC cells were also evaluated by utilizing the MTT assay. Then, apoptosis detection was performed by Annexin V/PI-flow cytometry (FC). Besides, the DNA fragmentation analysis was conducted utilizing agarose gel electrophoresis (AGE). Bcl-2, Bax, and CASP3 expression levels in PANC-1 cells using western blot analysis and qRT-PCR.

RESULTS

Herein, DPPH IC50 values for M. sativa extracts (water, MeOH, EtOH) were 76.21, 110.32, and 65.39 μg/ml, respectively. The water extract of M. sativa exhibited the highest TPC (4612.15 ± 119.4 mgGAE/g). The cytotoxicity IC50 values for EtOH M. sativa extract, GEM, and combined GEM with EtOH M. sativa on PANC1 cells were 68.74, 43.53, and 41.22 µg/ml M. sativa + 25 µg/ml GEM, respectively, with no toxicity observed in HUVEC cells. FC analysis revealed that Combining GEM and EtOH M. sativa yielded the highest apoptosis rate (25.6%). Expression changes in Bcl-2, Bax, and CASP3, as well as morphological alterations and DNA fragmentation, indicated apoptotic cell death.

CONCLUSION

Our findings suggested that combining M.sativa EtOH extracts with GEM may represent a promising strategy for treating PC.

摘要

引言

胰腺癌（PC）预后较差，对治疗的反应有限。组合疗法，如基于天然产物的疗法，可以提高抗癌疗效，同时将副作用降至最低。本研究评估了苜蓿的抗癌特性及其作为吉西他滨（GEM）辅助疗法使PANC-1细胞对化疗敏感的潜力。

方法

采用DPPH自由基清除法评估苜蓿提取物（甲醇、乙酸乙酯和水）的抗氧化活性（AA）和总酚含量（TPC）。还通过MTT法评估对PANC1和HUVEC细胞的细胞毒性作用。然后，通过膜联蛋白V/PI流式细胞术（FC）进行凋亡检测。此外，利用琼脂糖凝胶电泳（AGE）进行DNA片段化分析。使用蛋白质免疫印迹分析和qRT-PCR检测PANC-1细胞中Bcl-2、Bax和CASP3的表达水平。

结果

在此，苜蓿提取物（水、甲醇、乙醇）的DPPH IC50值分别为76.21、110.32和65.39μg/ml。苜蓿水提取物的TPC最高（4612.15±119.4mg GAE/g）。乙醇苜蓿提取物、GEM以及乙醇苜蓿提取物与GEM联合对PANC1细胞的细胞毒性IC50值分别为68.74、43.53和41.22μg/ml苜蓿+25μg/ml GEM，在HUVEC细胞中未观察到毒性。FC分析显示，GEM与乙醇苜蓿提取物联合产生的凋亡率最高（25.6%）。Bcl-2、Bax和CASP3的表达变化以及形态改变和DNA片段化表明细胞凋亡死亡。

结论

我们的研究结果表明，将苜蓿乙醇提取物与GEM联合使用可能是治疗胰腺癌的一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec13/12290208/36fe06917335/APJCP-26-1689-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec13/12290208/b1b8ca9ebe2e/APJCP-26-1689-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec13/12290208/36fe06917335/APJCP-26-1689-g007.jpg

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