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

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.

To Explore the Effects of Acupuncture and Medical Treatment at Different Times on the Gastrointestinal Reaction and White Blood Cell Count of Patients with Lung Cancer Chemotherapy

“…The results confirmed that compared with the treatment of tropisetron hydrochloride alone, the combined acupuncture treatment can improve the life quality of the patients to a greater extent, which is beneficial to the improvement of the patient's physical function status, and the patient's self-confidence in treatment is significantly improved. The patient was treated with chemotherapy, and the side effects and white blood cell count decreased significantly [ 20 – 22 ]. The results of combined acupuncture and drug treatment showed that the white blood cell counts of the three groups were significantly reduced after treatment, but the difference between the groups was not statistically significant ( P > 0.05).…”

Transcriptome Analysis Reveals the Anti-Tumor Mechanism of Eucalyptol Treatment on Neuroblastoma Cell Line SH-SY5Y

“…Moxibustion is an effective supportive cancer care in inhibiting tumor growth [25,26] and alleviating side effects of chemotherapy and radiotherapy [27]. Such as, moxibustion can inhibit nausea and vomiting after chemotherapy…”

Clinical Efficacy and Potential Mechanisms of Acupoint Stimulation Combined With Chemotherapy in Combating Cancer: A Review and Prospects

“…Our previous study also showed that cisplatin inhibited all leukocyte subpopulations and was more detrimental to T lymphocytes than to B lymphocytes in xenograft mice. This indicates the potential of cisplatin to induce immunosuppression and limit antitumor immune responses ( 61 ). Based on the fact that acupoint stimulation can improve myelosuppression and immunosuppression caused by cisplatin, and BM hematopoiesis is an important source of immune cell subgroups in the tumor immune microenvironment (TIME), we speculate that acupoint stimulation may contribute to the inhibition of tumor growth and the improvement of the TIME via recovery of BM hematopoiesis.…”

“…Basic research on the tumor-inhibiting effects and mechanisms of acupoint stimulation has also been conducted. In this review, we retrieved seven basic studies, which showed that acupoint stimulation with chemotherapy could delay tumor growth and metastasis to some extent in mice with breast cancer ( 60 , 62 ), osteosarcoma ( 63 , 64 ), colon cancer ( 65 ), and non-small cell lung cancer ( 61 ) models and could prolong survival in mice (shown in Table 4 ).…”

“…Our previous study ( 61 ) used moxibustion at the ST36 acupoint combined with cisplatin chemotherapy in LLC mice and found that the tumor-suppressive effect of moxibustion combined with cisplatin chemotherapy was superior to that of chemotherapy alone or moxibustion alone. It was further observed that moxibustion upregulated the infiltration of CD4 + T cells and Th1 cells in tumors and that the combination therapy increased the expression of CD8 + cytotoxic T cells, CD4 + T cells, Th1, Th9 cells, and M1 macrophages and genes expressing CD69, IFN-γ, and CD86.…”