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Introduction
Human osteosarcoma (OS) is the most commom primary malignant bone tumor, accounting for approximately 20% of all primary sarcomas in bone (1). Well-known for its metastasis and high local recurrence rate (2,3), osteosarcoma is a type of cancer whose treatment requires an extensive multimodal approach including surgery, radiotherapy and chemotherapy. Currently, chemotherapeutic regimens for human osteosarcoma treatment use the combination of multiple chemotherapeutic agents including high-dose methotrexate (HD-MTX) with leucovorin rescue, doxorubicin (adriamycin), cisplatin and ifosfamide either with or without etoposide (4). Although new therapies consisting of aggressive adjuvant chemotherapy and wide tumor excision have led to a significant benefit in terms of patients’ survival, the frequent acquisition of drug-resistant phenotypes and unwanted side-effects are often associated with chemotherapy and remain as serious problems (5). It is therefore urgent that new therapeutic strategies which can improve the effect of current chemotherapy be developed.
Chinese herbal medicine, a major modality in traditional Chinese medicine (TCM) and practiced for thousands of years in China and other Asian countries, is used for treating cancers (6–8). Herbal formulations are the common form of administration in Chinese herbal practice, and herbal formulas are well documented in ancient and modern literature (9,10). According to Chinese herbal theory, interactions among the different herbs in a formula exert a synergistic effect and neutralize potential toxicity and side-effects of the individual constituents (11,12). However, there is as yet a lack of rigorous scientific evaluation of such formulas.
The classical formula Xiao Jin Wan (XJW), formerly known as Xiao Jin Dan (XJD), first documented in the book Wai Ke Zheng Zhi Quan Sheng Ji (13), consists of ten component herbs, She Xiang (Moschus), Mu Bie Zi (Cochinchina momordica seed), Zhi Cao Wu (Radic aconiti Kusnezoffii preparata), Feng Xiang Zhi (Resina liquidambaris), Ru Xiang (Frankincense), Mo Yao (Myrrh), Dang Gui (Chinese angelica), Wu Ling Zhi (Trogopterus dung), Di Long (Pheretima) and Xiang Mo (Pine-soot ink). As a well-known traditional Chinese folk-medicine, it is used for eliminating stagnation, removing of blood stasis, promoting of blood circulation and alleviating pain (14), which is commonly used for treatment of various types of diseases including cancers, such as breast...