The anti-cancer efficacy of compound herbal formula, modified Liow-jiun-Tzyy-Tang, in murine tumor models

• Main Authors: Tsai-Feng Li, 李彩鳳
• Other Authors: Shu-Ling Fu
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/37825555030633252237

碩士 === 國立陽明大學 === 傳統醫藥研究所 === 101 === Cancer is the leading cause of death in Taiwan. At present, conventional therapies for cancer include surgery, chemotherapy and radiotherapy. Although these therapeutic strategies can improve survival of cancer patients, chemo- or radio-therapy-induced adverse effects and cancer relapse limit therapeutic outcome. Recently, using herbal medicine or its derived components as cancer therapeutic agents or as adjuvant for conventional therapy are getting much acceptance worldwide. Many patients undergoing cancer therapy consider complementary and alternative medicine options to reduce side effects and organ toxicity, to stimulate immunity, or to prevent further tumor progression or recurrence. However, scientific evidence regarding the efficacy and safety of herbs remains unclear. A compound herbal formula (modified Si-Jun-Zi Decoction; mSJZD) which could “reinforce the healthy qi” in traditional Chinese medicine theory has been used to improve the life quality of the outpatients widely. mSJZD contains seven herbs including Radix codonopsis, Atractylodes Rhizoma, Poria cocos, Radix Glycyrrhizae, Radix astragali, Herba pogostemonis and Fructus Ligustri Lucidi. Several herbs in mSJZD have been previously demonstrated to exhibit anti-cancer and immunomodulatory effects. In this study, we investigated the anti-tumor effects of mSJZD and its action mechanism in three types of murine xenograft tumor models. To investigate whether the anticancer activity of mSJZD involves activation of immune system, the expression of anti-cancer related cytokines in tumors was measured using ELISA, and the accumulation of tumor-infiltrating leukocytes at tumor sites was detected by qRT-PCR. To investigate whether the anticancer activity of mSJZD results from its cytostatic or/and cytotoxic effects on cancer cells, the tumor sections were analyzed with immunohistochemical staining of Ki67 for measuring cell proliferation and with TUNEL assays for detecting apoptosis. The protein expression of p53, p21, activated caspase 3, and cleaved PARP was also detected by Western blot. To confirm the tumor-suppressing effect, we assessed viability and proliferation index of cancer cells by MTT assay, PI staining, growth curve, and BrdU incorporation assay in vitro. The results showed that mSJZD treatment caused significant tumor regression in both immune-competent and immune-compromised mice inoculated with bladder or lung cancer cells without causing toxicity. The expression of anticancer-associated cytokines (IFN-, TNF-, IL-2, IL-12) and the presence of tumor-infiltrating leukocytes at tumor sites were not induced in immune-competent mice after mSJZD treatment. Our data indicated the anticancer activity of mSJZD mainly resulted from its inhibitory effects on cancer cells. Notably, the results of IHC-ki67 expression and TUNEL assay in tumor tissues indicated that mSJZD treatment reduced the proliferation of cancer cells but did not promote cancer cell apoptosis. Furthermore, the expression of tumor suppressor proteins, p21 and p53, was elevated in the tumor regions of mSJZD-treated mice. Besides, Co-treatment of mSJZD with chemotherapeutic drug doxorubicin did not show enhanced therapeutic effects or apparent toxicity. In vitro, mSJZD treatment suppressed the viability and proliferation of cancer cells, whereas had no inhibitory effects on normal cells (MEF). Together, these results indicated that mSJZD might cause cytostatic effects to suppress tumor growth, instead of immunomodulation effects. Currently, there are few literatures describing the pharmacological activity of mSJZD, and the present study is the first report on the anticancer activity of mSJZD in murine models. These findings provide mechanistic and pharmacological basis for the possible clinical application of mSJZD in cancer treatment. Certainly, more investigations are warranted to further explore the therapeutic potentials and action mechanisms of mSJZD for cancer therapeutics.