Study On The Anti-tumor Activity Of Chitosan-based Hydrogel

Chitosan is the unique alkaline polysaccharide in nature. It has extensive sourcesand abundant reserves, is widely utilized to synthesize many kinds of functionalbiomaterials for its excellent biocompatibility, biodegradability and adhesion. Thechitosan-based hydrogel (CH) used in this study, mainly made of modified chitosan, isa thermosensitive hydrogel, which takes the shortest time to gel at37℃, and can gelin situ. CH is applied in various fields such as drug-delivery systems and tissueengineering, however, its anti-tumor property is rarely reported. This research studiesthe anti-tumor activity in vitro and in vivo, then on the base of the results, develops afurther study of CH on anti-metastasis effects, so as to systematically state theanti-tumor effects of CH, providing evidences for the application of CH in tumortherapy and post-operation recovery.In vitro study, human liver cell L02, human hepatoma cell Bel-7402, humancervical carcinoma cell Hela and human gastric cancer cell SGC-7901are used toevaluate the cytotoxicity of CH by MTT assay, and the morphology of cells areobserved by inverted microscope. Transplant solid tumor models of Sarcoma180andHepatoma22are established in mice, and CH is administrated through intraperitonealinjection. Tumor inhibitory ratio, immune organ index, correlation factors levels aremeasured to investigate the anti-tumor activity of CH in vivo. Hepatoma metastasismodels of H22are established in mice, and CH is administrated throughintraperitoneal injection. Anti-metastasis effects are evaluated by pulmonary andlymphatic metastasis degrees and metastasis correlation factors levels.Results reveal that CH of certain concentration ranges, especially from0.001g·mL-1to0.005g·mL-1, could inhibite the proliferation of Bel-7402, Hela andSGC-7901cells, the lowest relative growth rate is80.40%, and promote theproliferation of L02cell, and the relative growth rates were all above80%, showingno cytotoxicity. In vivo, CH could significantly inhibite transplanted tumors of S180 and H22growth, and low-dose CH performed better, inhibition ratios are39.90%and47.47%, respectively. CH could increase immune organ index and cytokine levels ofTNF-α, IL-2and IFN-γ, kill tumor cells, lower VEGF level and restrain angiogenesis.Moreover, low-dose CH could notably decrease pulmonary and lymphatic metastasisdegrees and metastasis correlation factors levels of VEGF and E-selectin, expressesanti-metastasis effects.In conclusion, CH could inhibit tumor cells growth and promote the proliferationof normal cells to certain extend, showing good bio-safety; and enhance immunesystem function, inhibit tumor growth, infiltration and metastasis. Therefore, CHperforms good prospects in tumor removal surgery application.