Traditional Chinese Medicine Xihuang Wan Inhibited Lewis Lung Carcinoma in a Syngeneic Model, Equivalent to Cytotoxic Chemotherapy, by Altering Multiple Signaling Pathways

Abstract

Background/Aim: Xihuang Wan (XHW), a traditional Chinese medicine (TCM), has been used in China for a variety of cancers including lung cancer. The present study evaluated the efficacy of XHW on a Lewis lung mouse model and explored the potential mechanism via transcriptomics. Materials and Methods: The mice were randomized into 6 groups: 1) untreated control (n=10); 2) low-dose XHW; 3) medium-dose XHW; 4) high-dose XHW; 5) cisplatin; and 6) untreated blank (n=4). Lewis lung carcinoma (LLC) cells were injected subcutaneously except for the 4 mice in the blank group. The body weight and tumor length and width were measured every 3 days. RNAsequencing was performed on tumors in the high-dose XHW group and the control group. Results: XHW inhibited the growth of LLC in a syngeneic mouse model, without toxicity, with equivalent efficacy to cisplatin. RNA-sequencing demonstrated that many signaling pathways were involved in XHW-mediated inhibition of LLC, including tumor necrosis factor, estrogen, cyclic guanosine 3', 5'monophosphate-protein kinase G, apelin and the peroxisome proliferator-activated receptor signaling pathways. Conclusion: XHW inhibited LLC carcinoma through different pathways and shows clinical promise for patients who cannot tolerate platinum-based drugs.Lung cancer, with an estimated 2.2 million new cases and 1.8 million deaths in 2020, ranks second in incidence and first in mortality among all cancer types throughout the world (1). In China, lung cancer was also the second most commonly diagnosed cancer (815,563 cases) and the leading cause of cancer death (243,153 cases) in 2020 (2). First-line treatment includes surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy (3, 4). However, lung cancer still remains recalcitrant.In China, traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years for a variety of diseases, including benign and malignant tumors (5-8). Xihuang Wan (XHW) was first recorded in the 18 th -century Chinese medical book Waike Zhengzhi Quansheng Ji (Lifesaving Manual of Diagnosis and Treatment of External Diseases). XHW comprises Ruxiang (Olibanum), Moyao (Myrrha), Niuhuang (Moschus), and Shexiang (Bovis Calculus). XHW has been approved by the National Medical Products Administration (NMPA) of China for the treatment of cancer (approval number Z11020073). In clinical practice, XHW has been used to treat breast (9-12), colorectal (13), liver (14, 15), cervical (16-18), and lung cancer (19)(20)(21). A systematic review and meta-analysis showed that XHW combined with chemotherapy enhanced response, prolonged overall survival, improved the quality of life of patients, and alleviated treatment-induced side effects (22).Our laboratory has previously studied Lewis-lung carcinoma (LLC) in both nude mouse and syngeneic models (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). In the present study, we examined the anti-cancer efficacy of XHW in a syngeneic mouse model of LLC, and explored the potential mechanism of XHW by RNAsequencing...

Traditional Chinese Medicine JianPiHuaTan formula improving quality of life and survival in patients with colorectal cancer through RAS/RAF downstream signaling pathways

“…TCM treatment, derived from the medical system of Chinese civilization through extensive clinical practice and accumulated experience, uniquely focuses on comprehensive regulation of the body's internal environment to improve disease symptoms and enhance patient quality of life (Zhang et al, 2020b). Changes in the internal environment may affect the expression and regulation of specific genes, thereby influencing multiple aspects of cellular signal transduction and metabolic pathways (Chen et al, 2020;Zhang et al, 2021). Therefore, conducting research on the impact of TCM treatment on the transcriptome helps us gain insight into the efficacy and mechanisms of TCM treatment, providing a scientific basis for the clinical application of TCM.…”