Tumor Inhibition Effects and Mechanisms of Angelica sinensis and Sophorae flavescentis ait Decoction Combined with Cisplatin in Xenograft Mice

Background: To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophoraeflavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP). Materials and
Methods:Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP onH22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA methodfor serum HIF-1α, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied.
Results: Compared withDDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP,ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with othergroups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKPincreased significantly in DDP control group (p<0.01), while serum HIF-1α was increased in the model controlgroup. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased inall treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDPgroups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statisticaldifferences between the DDP and ASSF-DDP groups (p<0.01).
Conclusions: ASSF can inhibit bodyweight decreasecaused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-1αand pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutantp53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into bloodand enhancing thymus protection.