Arsenic Trioxide Injection In The Treatment Of Pancreatic Cancer In Experimental And Clinical Studies

Object: To study the theoretical foundation , the molecular mechanism and the clinical effect of AS2O3 injection for treating pancreatic carcinoma.Methods: (1) Theoretical studies: It was proved that the feasibility of As2O3 Injection for treating pancreatic carcinoma by studying the mechanism of "fighting poison with poison "and the experimental and clinical research of AS2O3 treating malignant tumor. (2) Experimental studies: Human pancreatic carcinoma cell line PC-3 was treated with As2O3 in various given concentrations, then its growth was analyzed by MTT assay; the As2O3's influence on the ratio of apoptosis and the growth cycle was investigated by the flow cytometer; And It was observed that the change of it's ultrastructure by electron microscope; By the Immunohistochemical staining , It was observed the expression of proteins (Fax, Fax-L, Bcl-2, Bax, CD44 and nm23) that are correlative with apoptosis and metastasis. (3 ) clinical research: By treating 8 patients of advanced pancreatic carcinoma with As2O3 injection, It was d known that the As2O3 injection treatment effect of pancreatic carcinoma patients with observing the change of life of quality (QOL), cancer ache and side effect of As2O3.Result: (1) Basic research show that the pathogenesis of malignancy is especially related to the cancerous toxins; the cancerous toxins are the pathological basis for the occurrence of pancreatic carcinoma; phlegm, dampness and stagnation are the pathological products in the course of the development of pancreatic carcinoma, and deficiency of the antipathogenic factors were the inherent factors for the occurrence and development of pancreatic carcinoma. These factors had a causal relationship among themselves, leading to the characteristic complexity in the pathogenesis of pancreatic carcinoma. The theoretical basis for the anti-cancer effect of arsenic drug were "treating the toxifying diseases with poisonous agents" , "resolving phlegm to soften hard masses "and "removing the necrotic tissue and eroding the sores." As2O3 injection has been used effectively in the clinical practice for APL , hepatocelluar carcinoma ect. ( 2 Experimental studies: As2O3 could inhibit the growth of PC-3 cells. AS2O3 also could induce the apoptosis and hold the cell cycle of PC-3 cells on S phase. Immunohistochemical staining showed that As2O3 could make the expression of Bcl-2, CD44 up and make the expression of Fax , Fax-L, nm23 down. (3) Clinicalresearch: As2O3 injection can release the patient 's cancer ache, control cancer fever and improve the QOL. The clinical efficacy of As2O3 injection is obvious with fewer side effects.Conclusion: The anti-tumor effect of As2O3 is supported by not only the traditional Chinese medicine theory but the also the modern experiment studies and clinical application. As2O3 injection can obliviously induce human pancreatic carcinoma cell apoptosis and inhibit pancreatic carcinoma metastasis. The mechanism probably is that As2O3 could change the expression of Fax , Fax-L, Bel-2 , CD44 and nm23 genes .This study has a very important theoretical significance and practical value to find out the mechanism that Chinese traditional medicine Pishuang for treating pancreatic carcinoma by molecular biology technology and to promote the clinical practice. It also has great reference value for other study of new anti-tumor drugs uncovered from traditional Chinese medicine.