Xiao-Ai-Ping, a TCM Injection, Enhances the Antigrowth Effects of Cisplatin on Lewis Lung Cancer Cells through Promoting the Infiltration and Function of CD8+ T Lymphocytes

Li Ws, Yang Y, Ouyang Zj, et al. Evidence-Based Complementary and Alternative Medicine. Volume 2013 (2013) http://dx.doi.org/10.1155/2013/879512


To investigate how Xiao-Ai-Ping injection, a traditional Chinese medicine and an ancillary drug in tumor treatment, enhances the antitumor effects of cisplatin on Lewis lung cancer (LLC) cells.

LLC-bearing mice were daily intraperitoneally injected with various doses of cisplatin, Xiao-Ai-Ping, or cisplatin plus Xiao-Ai-Ping, respectively. Body weight and tumor volumes were measured every three days.

Combination of Xiao-Ai-Ping and cisplatin yielded significantly better antigrowth and proapoptotic effects on LLC xenografts than sole drug treatment did. In addition, we found that Xiao-Ai-Ping triggered the infiltration of CD8+ T cells, a group of cytotoxic T cells, to LLC xenografts. Furthermore, the mRNA levels of interferon-? (ifn-?), perforin-1 (prf-1), and granzyme B (gzmb) in CD8+ T cells were significantly increased after combination treatment of Xiao-Ai-Ping and cisplatin. In vitro studies showed that Xiao-Ai-Ping markedly upregulated the mRNA levels of ifn-?, prf-1, and gzmb in CD8+ T cells in a concentration-dependent manner, suggesting that Xiao-Ai-Ping augments the function of CD8+ T cells.

Xiao-Ai-Ping promotes the infiltration and function of CD8+ T cells and thus enhances the antigrowth effects of cisplatin on LLC xenografts, which provides new evidence for the combination of Xiao-Ai-Ping and cisplatin in clinic in China

Chemotherapy is one of the key tools used in tumor treatment [1-3], and whether chemotherapy drugs promote antitumor immunity is one of the crucial factors that determine the effects of the drugs [4-8]. Plant-derived natural products play an important role in cancer chemotherapy. Numerous molecules, such as paclitaxel, vincristine, camptothecin, and epipodophyllotoxin, are invaluable contributions of nature to modern medicine [9]. In recent years, interest in using natural products as therapeutic agents for cancer has sharply increased [1,10-14]. Thus, the quest to search for novel therapeutic compounds or strategies for cancer treatment and management is a never-ending venture.Marsdenia tenacissima, the stem of Marsdenia tenacissima (Roxb.) Wight et Arn. (Asclepiadaceae Family), is widely grown in the southern provinces of China [1]. More than 40 C-21 steroidal glycosides have been isolated from Marsdenia tenacissima [15], some of which were proved to show cytotoxic activities against cancer cells [16]. Xiao-Ai-Ping injection, a standard M. tenacissima extract, is shown to be clinically effective in treatment of NSCLC when combined with chemotherapeutics agents [17-19]. However, the exact mechanism of the combination strategy remains vague. In the present study, we demonstrate that Xiao-Ai-Ping promotes the infiltration and function of CD8+ cytotoxic T cells and thus enhances the antigrowth effects of cisplatin on mouse Lewis lung cancer cells. Our data provide the molecular theoretical basis for clinical application of Xiao-Ai-Ping injection in patients with NSCLC.

The current study demonstrates for the first time that Xiao-Ai-Ping promotes the infiltration and function of CD8+ cytotoxic T cells and modulates the immune system in tumor-bearing mice and thus enhances the anticancer effect of cisplatin. The present study gives a theoretical support for the clinical use of Xiao-Ai-Ping injection in patients with NSCLC.

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