OncoTargets and Therapy (Nov 2019)

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

  • Zhang Y,
  • Ge T,
  • Xiang P,
  • Zhou J,
  • Tang S,
  • Mao H,
  • Tang Q

Journal volume & issue
Vol. Volume 12
pp. 9725 – 9734

Abstract

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Yonggang Zhang,1 Tingrui Ge,1 Ping Xiang,1 Jingyi Zhou,1 Shumin Tang,1 Haibing Mao,1 Qiang Tang2 1Department 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; 2Department of Gastrointestinal Surgery, The First People’s Hospital of Lianyungang, Xuzhou Medical University Affiliated Hospital of Lianyungang, Lianyungang, Jiangsu 222061, People’s Republic of ChinaCorrespondence: Qiang TangDepartment of Gastrointestinal Surgery, The First People’s Hospital of Lianyungang, Xuzhou Medical University Affiliated Hospital of Lianyungang, No. 18 Tongguan Road, Xinpu District, Lianyungang, Jiangsu 222061, People’s Republic of ChinaEmail [email protected]: 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.Keywords: colorectal cancer, tanshinone IIA, oxaliplatin, Akt/ERK signaling pathway  

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