Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

Jianxiao Zheng; Gong Li; Juanjuan Wang; Shujing Wang; Qing Tang; Honghao Sheng; Wanyin Wu; Sumei Wang

doi:10.3389/fphar.2021.753068

Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

Front Pharmacol. 2021 Dec 9:12:753068. doi: 10.3389/fphar.2021.753068. eCollection 2021.

Authors

Jianxiao Zheng^{1

2}, Gong Li², Juanjuan Wang³, Shujing Wang⁴, Qing Tang^{1

3}, Honghao Sheng^{1

3}, Wanyin Wu^{1

3}, Sumei Wang^{1

3}

Affiliations

¹ Department of Oncology, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China.
² Department of Radiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
³ State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁴ The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

Abstract

Background: Radiation-induced skin injury is a major side-effect observed in cancer patients who received radiotherapy. Thus identifying new radioprotective drugs for prevention or treatment of post-irradiation skin injury should be prompted. A large number of clinical studies have confirmed that Compound Kushen injection (CKI) can enhance efficacy and reduce toxicity of radiotherapy. The aim of this study is to confirm the effect of CKI in alleviating radiotherapy injury in the skin and explore the exact mechanism. Methods: 60 patients who met the inclusion/exclusion criteria were allocated to treatment group (CKI before radiotherapy) or control group (normal saline before radiotherapy) randomly. MTT assay, flow cytometry, Western Blot, and transient transfection were performed to detect the cell viability, cell apoptosis and Bim expression after treatment with CKI or/and radiotherapy. Results: CKI had the effect of alleviating skin injury in cancer patients who received radiotherapy in clinic. CKI induced cancer cell apoptosis when combined with irradiation (IR), while it reversed the induction of cell apoptosis by IR in human skin fibroblast (HSF) cells. And Bim, as a tumor suppressor, was induced in cancer cells but had no change in HSF cells when treated with CKI. Moreover, the above effect could be attenuated when Bim was silenced by siRNA. Conclusion: We conclude that CKI represents a promising radio-protective agent with a potential differential beneficial effect on both cancer cells (inducing apoptosis) and HSF cells (providing radio-protection via inhibiting IR-induced apoptosis), via regulating Bim. Our study uncovers a novel mechanism by which CKI inhibits human cancer cell while protects skin from radiotherapy, indicating CKI might be a promising radio-protective drug. Clinical Trial Registration: Chinese Clinical Trial Registry (www.chictr.org.cn), identifier ChiCTR2100049164.

Keywords: Bim; cancer; compound kushen injection; radiation injury; skin.