The Combinatorial Effect of Cisplatin and Moxibustion on Tumor Growth Inhibition with Special Reference to Modulation of the Immune Microenvironment in Lewis Lung Cancer Mice

Bin Wang; Jin Huang; Shanshan Li; Zhanyu Pan; Yongming Guo; Yinli Yang; Ling Li; Cong Wang; Yinan Gong; Jiaqi Wang; Shanshan Lu; Zhifang Xu; Yi Guo

doi:10.1155/2020/3170803

The Combinatorial Effect of Cisplatin and Moxibustion on Tumor Growth Inhibition with Special Reference to Modulation of the Immune Microenvironment in Lewis Lung Cancer Mice

Evid Based Complement Alternat Med. 2020 Dec 29:2020:3170803. doi: 10.1155/2020/3170803. eCollection 2020.

Authors

Bin Wang^{1

2}, Jin Huang², Shanshan Li², Zhanyu Pan¹, Yongming Guo^{2

3}, Yinli Yang¹, Ling Li¹, Cong Wang¹, Yinan Gong², Jiaqi Wang², Shanshan Lu², Zhifang Xu^{2

3}, Yi Guo^{2

4}

Affiliations

¹ Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
² Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
³ School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
⁴ School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Abstract

Objective: As a first-line treatment for non-small cell lung cancer (NSCLC), the efficacy of chemotherapy is still unsatisfactory. Moxibustion has been shown to improve the side effects of radiotherapy and chemotherapy and regulate immune function. This study aimed to explore the antitumor effects and potential mechanisms of combinatorial cisplatin and moxibustion treatment for NSCLC by targeting the tumor microenvironment.

Methods: Lewis lung cancer (LLC)-bearing mice were induced and treated with cisplatin or/and moxibustion at ST36 (Zusanli), and the growth, weight, and area of the tumor were evaluated. The numbers of various T cell subsets and myeloid cells in the tumor were assessed by flow cytometry, and the gene expression of related markers and cytokines was detected with real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the tumor vascular structure was investigated using CD31 and α-smooth muscle actin (α-SMA) immunofluorescence staining. The expression of the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) was detected by immunohistochemical staining.

Results: Both cisplatin and moxibustion inhibited LLC tumor growth and reduced both the tumor area and weight, with the combinatorial therapy showing superior outcomes. Moxibustion upregulated the infiltration of CD4⁺ T cells and Th1 cells in the tumor, and the combinatorial therapy increased the proportion of CD8⁺ cytotoxic T cells (CTLs), CD4⁺T cells, Th1, Th9 cells, and M1 macrophages, as well as the expression of Cd69, Ifng, and Cd86 mRNA. The combinatorial therapy improved vascular normalization by increasing both the microvessel density (MVD) and pericyte coverage (α-SMA area density) and inhibiting the expression of the VEGF.

Conclusions: Combinatorial cisplatin and moxibustion treatment inhibited the LLC tumor growth by mechanisms related to the improvement of the tumor immune microenvironment and vascular normalization, providing an effective combinatorial therapy beneficial for patients with NSCLC.