Antitumor activity of yulangsan polysacchrides in mice bearing S180 sarcoma tumors

Abstract

Abstract. Sarcoma is one of the most prevalent pediatric tumors and the therapeutic role of chemotherapy has yet to be elucidated. It has been reported that extracts of Longyanshen (Yulangsan) may enhance the sensitivity of drug-resistant cancer cell lines, and improve the immune dysfunction induced by cyclophosphamide (CTX) in mice. The present in vivo study investigated the antitumor effects of Yulangsan polysaccharides (YLSPS) and their interaction with CTX in murine sarcoma 180 (S180)-bearing mice. Immunohistochemistry was used to detect the expression of apoptosis-related proteins. The ultrastructure of sarcoma cells was examined by transmission electron microscopy and the tumor growth rate was determined by measuring the tumor weight. A dose-dependent inhibition of sarcoma growth was observed in S180-bearing mice following administration of YLSPS. In combination with CTX, an additive antitumor effect was obtained, which was accompanied by amelioration of immune function. YLSPS also potentiated the tumor suppression effect of CTX while avoiding cytotoxicity against immune cells. YLSPS inhibited sarcoma growth in S180-bearing mice through the induction of apoptosis in S180 sarcoma cells. YLSPS also attenuated CTX-induced cytotoxicity to the immune system while potentiating the tumor suppression effect. These results provide additional information regarding combination therapy with YLSPS and chemotherapy for the treatment of sarcoma. IntroductionSarcomas are a heterogeneous group of tumors that are mesenchymal in origin and account for 1% of adult tumors and 15% of pediatric tumors (1,2). Approximately 80% of sarcomas originate from soft tissue and 20% from bone. Similar to other types of solid tumors, conventional therapy includes surgery, radiotherapy and chemotherapy. The role of adjuvant or neoadjuvant chemotherapy for sarcoma has not yet been fully elucidated, as large prospective analyses have not demonstrated their unequivocal benefit (3,4); however, a previous meta-analysis suggested that adjuvant chemotherapy is associated with a moderate overall survival advantage (5). A number of agents are currently used for sarcoma therapy, including doxorubicin, ifosfamide, dacarbazine, cisplatin, vincristine, cyclophosphamide (CTX) and etoposide. Under most circumstances, the combination of ≥2 agents is commonly used in patients with sarcoma, as combination chemotherapy appears to increase response rates; however, it is associated with greater toxicity, with immunosuppression being one of the most serious side effects, with no overall survival advantage (6).Yulangsan, also referred to as Longyanshen, is a commonly used herb in the indigenous Zhuang community in Guangxi, China, and is derived from the dried roots of Millettia pulchra Kurz var-laxior (Dunn) Z. We. Locally, this herb is used for patients recuperating after illness and those concerned about their general health. In the published literature, it has been reported that Yulangsan may enhance the function of the immune system (7). Kong et al found that ...