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伊达比星-菠萝蛋白酶联合用药使癌细胞对传统化疗更敏感。

Idarubicin-bromelain combination sensitizes cancer cells to conventional chemotherapy.

作者信息

Taşkın Abdullah, Tarakçıoğlu Mehmet, Ulusal Hasan, Örkmez Mustafa, Taysı Seyithan

机构信息

Nutrition and Dietetics Department, Faculty of Health Science, Harran University, Şanlıurfa, Turkey.

Department of Biochemistry, Medical Faculty, Gaziantep University, Gaziantep, Turkey.

出版信息

Iran J Basic Med Sci. 2019 Oct;22(10):1172-1178. doi: 10.22038/ijbms.2019.37884.9003.

Abstract

OBJECTIVES

The primary cytotoxic effects of anticancer drugs like idarubicin, a chemotherapeutic agent, are not limited to neoplastic cells; they also produce similar effects in normal cells. In this study, we hypothesized that the combination of idarubicin-bromelain could make cancer cells more susceptible to cytotoxicity and genotoxicity.

MATERIALS AND METHODS

To test our hypothesis, the optimal concentrations of idarubicin and bromelain were combined and incubated in the HL-60 cancer cell line and normal human mononuclear leukocytes (PBMC) for 24, 48, and 72 hr. Cytotoxicity and genotoxicity were evaluated by measurement of ATP cell viability test, DNA damage, Caspase-3, Acridine orange/ethidium bromide (AO/EB), and DAPI fluorescent dyes in both cell types.

RESULTS

The combination of idarubicin-bromelain significantly reduced cell proliferation in the more potent HL-60 compared to PBMC in all incubation times (0.05). DNA damage and Caspase-3 levels (except for 24 hr) were also higher in the HL-60 cell line in comparison with PBMC and were statistically significant (0.05). The percentages of apoptotic images obtained by DAPI and AO / EB morphological examination were increased in both cells, depending on the combination dose.

CONCLUSION

Based on these results, it can be concluded that idarubicin combined with bromelain produces more cytotoxic effects in low concentrations in comparison with when it was used per se in the HL-60 cells. Conversely, it was found that this combination in PBMC caused less cytotoxicity and less genotoxicity. Taken together, it can be said that this new combination makes cancer cells more sensitive to conventional therapy.

摘要

目的

抗癌药物如伊达比星(一种化疗药物)的主要细胞毒性作用并不局限于肿瘤细胞;它们在正常细胞中也会产生类似作用。在本研究中,我们假设伊达比星与菠萝蛋白酶联合使用可使癌细胞对细胞毒性和基因毒性更敏感。

材料与方法

为验证我们的假设,将伊达比星和菠萝蛋白酶的最佳浓度组合,并在HL-60癌细胞系和正常人外周血单个核白细胞(PBMC)中孵育24、48和72小时。通过测量两种细胞类型中的ATP细胞活力试验、DNA损伤、半胱天冬酶-3、吖啶橙/溴化乙锭(AO/EB)和DAPI荧光染料来评估细胞毒性和基因毒性。

结果

在所有孵育时间内,与PBMC相比,伊达比星-菠萝蛋白酶组合在更具活性的HL-60细胞中显著降低了细胞增殖(P<0.05)。与PBMC相比,HL-60细胞系中的DNA损伤和半胱天冬酶-3水平(24小时除外)也更高,且具有统计学意义(P<0.05)。根据联合剂量的不同,通过DAPI和AO/EB形态学检查获得的两种细胞凋亡图像的百分比均有所增加。

结论

基于这些结果,可以得出结论,与单独使用伊达比星相比,其与菠萝蛋白酶联合使用在低浓度下对HL-60细胞产生了更强的细胞毒性作用。相反,发现该组合在PBMC中引起的细胞毒性和基因毒性较小。综上所述,可以说这种新组合使癌细胞对传统疗法更敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971b/6885387/24b263a55004/IJBMS-22-1172-g001.jpg

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