Clinical Distribution and Molecular Basis of Traditional Chinese Medicine ZHENG in Cancer

Abstract

In traditional Chinese medicine (TCM) clinical practice, ZHENG (also known as syndrome) helps to guide design of individualized treatment strategies. In this study, we investigated the clinical use of ZHENG in TCM-treated cancer patients by systematically analyzing data from all relevant reports in the Chinese-language scientific literature. We aimed to determine the clinical ZHENG distributions in six common cancers (lung, liver, gastric, breast, colorectal, and pancreatic) with the expectation of uncovering a theoretical basis for TCM ZHENG as a clinical cancer treatment. In addition, we also reviewed the molecular basis underlying Xue-Yu (blood stasis), Shi-Re (dampness-heat), Yin-Xu (Yin deficiency), and Pi-Xu (spleen deficiency) ZHENG that are commonly found in cancer patients. The results from our summary study provide insights into the potential utility of TCM ZHENG and may contribute to a better understanding of the molecular basis of TCM ZHENG in cancer.

Figure 1

Annual publications on TCM ZHENG in cancer. (a) A total of 2175 papers were retrieved by searching the terms “Zhong Yi” (traditional Chinese medicine), “ZHENG,” and “Ai” (cancer) through the main Chinese electronic databases, including China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Wanfang Database, and Chinese BioMedical Literature Database (CBM), and then analyzed by calculating the annual publications from January 1, 2000 to November 13, 2011. (b) The distributions of cancer types among all the publications. *To November 13, 2011.

Figure 2

Clinical distributions of TCM ZHENG in common cancers. Annual publications for each common cancer were calculated and presented as a histogram. Publications involved with clinical trials and case series, where information on more than 10 cases with ZHENG description was available, were further selected. Thirty-two articles reported on lung cancer, 26 on liver cancer, 19 on gastric cancer, 21 on breast cancer, 29 on colorectal cancer, and 17 on pancreatic cancer. Finally, for each type of cancer, the distribution frequency of ZHENG was calculated and presented in pie chart. Note: Qi-Yin-Liang-Xu, deficiency of both Qi and Yin; Fei-Pi-Qi-Xu, lung-spleen Qi deficiency; Yin-Xu-Nei-Re, Yin asthenia and internal heat; Tan-Re, phlegm-heat; Xue-Yu, blood stasis; Pi-Xu, spleen deficiency; Gan-Shen-Yin-Xu, liver-kidney Yin deficiency; Qi-Zhi, Qi stagnation; Gan-Dan-Shi-Re, liver-gallbladder dampness-heat; Yu-Du-Zu-Zhi, stagnation of blood stasis and toxin; Gan-Wei-Bu-He, liver-stomach disharmony; Qi-Xue-Liang-Xu, deficiency of both Qi and blood; Yin-Xu-Nei-Re, Yin deficiency due to stomach heat; Tan-Shi-Nei-Zu, stagnation of phlegm-dampness; Gan-Qi-Fan-Wei, liver Qi invading stomach; Shi-Re-Yun-Jie, stagnation of dampness-heat; Pi-Shen-Yang-Xu, asthenic splenonephro-yang; Yu-Du-Nei-Zu, stagnation of blood stasis and toxin; Han-Shi-Kun-Pi, cold-dampness disturbing spleen.

Figure 3

A schematic cartoon portraying the molecular basis of Shi-Re ZHENG in pancreatic cancer, based on our previous studies. It has been proposed that tumors with Shi-Re ZHENG exhibited altered cancer-associated myofibroblast (CAF) proliferative activities and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines (such as SDF-1, VEGF, TGF-1β, IL-6, CCL3, CCL4, CCL5, TNF-α, IL-8, and bFGF). The presence of Shi-Re ZHENG has impact on tumor growth. Chinese herbs for Qing-Re-Hua-Shi (removing heat and dampness) inhibited cancer cell proliferation, invasion, and in vivo metastasis through modification of the tumor microenvironment. Cytokines that are marked in bold have been confirmed by our previous studies.