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丹参酮IIA通过抑制ERK/Akt信号通路逆转人结直肠癌对奥沙利铂的耐药性。

Tanshinone IIA Reverses Oxaliplatin Resistance In Human Colorectal Cancer Via Inhibition Of ERK/Akt Signaling Pathway.

作者信息

Zhang Yonggang, Ge Tingrui, Xiang Ping, Zhou Jingyi, Tang Shumin, Mao Haibing, Tang Qiang

机构信息

Department of Anus and Intestine Surgery, The First People's Hospital of Lianyungang, Xuzhou Medical University Affiliated Hospital of Lianyungang, Lianyungang, Jiangsu, 222061, People's Republic of China.

Department of Gastrointestinal Surgery, The First People's Hospital of Lianyungang, Xuzhou Medical University Affiliated Hospital of Lianyungang, Lianyungang, Jiangsu 222061, People's Republic of China.

出版信息

Onco Targets Ther. 2019 Nov 14;12:9725-9734. doi: 10.2147/OTT.S217914. eCollection 2019.

Abstract

BACKGROUND

Oxaliplatin (OXA)-based chemotherapy is generally used to treat human cancers, whereas OXA resistance is a main obstacle for the treatment of colorectal cancer (CRC). Evidence has shown that tanshinone IIA (Tan IIA) could induce apoptosis in CRC cells. However, the role of combination of OXA and Tan IIA on OXA-resistance CRC cells remains unknown. Thus, this study aimed to investigate the effects of Tan IIA in combination with OXA on OXA-resistance CRC cells.

METHODS

MTT assay, Ki67 immunofluorescence staining and flow cytometry were used to detect viability, proliferation and apoptosis in OXA-resistant cell line SW480/OXA, respectively. The expressions of Bcl-2, Bax, active caspase 3, p-Akt and p-ERK in SW480/OXA cells were detected with Western blot. In vivo animal study was performed finally.

RESULTS

In this study, the inhibitory effects of OXA on the proliferation and invasion of SW480/OXA cells were significantly enhanced by Tan IIA. In addition, Tan IIA obviously enhanced the anti-apoptosis effects of OXA on SW480/OXA cells via decreasing the levels of Bcl-2, p-Akt and p-ERK, and increasing the levels of Bax and active caspase 3. In vivo experiments confirmed that Tan IIA enhanced OXA sensitivity in SW480/OXA xenograft model.

CONCLUSION

We found that Tan IIA could reverse OXA resistance in OXA-resistance CRC cells. Therefore, OXA combined with Tan IIA might be considered as a therapeutic approach for the treatment of OXA-resistant CRC.

摘要

背景

基于奥沙利铂(OXA)的化疗通常用于治疗人类癌症,而奥沙利铂耐药是结直肠癌(CRC)治疗的主要障碍。有证据表明,丹参酮IIA(Tan IIA)可诱导CRC细胞凋亡。然而,奥沙利铂与丹参酮IIA联合作用于奥沙利铂耐药CRC细胞的作用尚不清楚。因此,本研究旨在探讨丹参酮IIA联合奥沙利铂对奥沙利铂耐药CRC细胞的影响。

方法

采用MTT法、Ki67免疫荧光染色和流式细胞术分别检测奥沙利铂耐药细胞系SW480/OXA的活力、增殖和凋亡情况。用蛋白质免疫印迹法检测SW480/OXA细胞中Bcl-2、Bax、活化的半胱天冬酶3、p-Akt和p-ERK的表达。最后进行体内动物实验。

结果

在本研究中,丹参酮IIA显著增强了奥沙利铂对SW480/OXA细胞增殖和侵袭的抑制作用。此外,丹参酮IIA通过降低Bcl-2、p-Akt和p-ERK水平,增加Bax和活化的半胱天冬酶3水平,明显增强了奥沙利铂对SW480/OXA细胞的抗凋亡作用。体内实验证实,丹参酮IIA增强了SW480/OXA异种移植模型中奥沙利铂的敏感性。

结论

我们发现丹参酮IIA可逆转奥沙利铂耐药CRC细胞中的奥沙利铂耐药性。因此,奥沙利铂联合丹参酮IIA可能被视为治疗奥沙利铂耐药CRC的一种治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27fc/6859961/76a74f37e61f/OTT-12-9725-g0001.jpg

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本文引用的文献

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The RNA-Binding Protein HuR Confers Oxaliplatin Resistance of Colorectal Cancer By Upregulating CDC6.
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