The Synergistic Antitumor Effects Of Berberine α-hydroxy δ-decanoylethyl Sulfonate With Other Chemotherapeutic Drugs And Its Antimetastatic Activity As Well As The Inhibition On Buccal Cancer Development In Hamster

Objective:To explore the synergistic antitumor effects of HB(berberineα-hydroxyβ-decanoylethyl sulfonate)with other chemotherapeutic drugs in vivo and in vitro, and its correlative mechanism;investigate the inhibition of HB on tumor metastasis and its mechanism;the inhibition of HB is to be evaluated on tumor development by buccal cancer hamster model.Methods:(1) MTT assay was employed to determine the cytotoxicity of HB combination with clinical chemotherapeutic drugs in tumor cells culture in vitro,such as HepG2, MGC80-3, SW480 cells. (2) HB was administrated to treat mice transplanted solid tumors H22 and S180 with 5-FU. (3) The inhibitory effects on topoisomerases was measured by supercoiled DNA relaxation assay.(4) Cell-matrix adhesion assay was used to study the adhesive ability of B16 cells. (5) The effects of HB on B16 cells'migration on Fibronection was observed by erasion trace test. (6) Transwell chamber assay was applied to measure the effect of HB on invasion of B16 cells. (7) Detect the expression of CD44V6 in tumor cell by immunohistochemical technique( S - P method) (8) The serious activity of MMP-2 and-9 of B16 was measured by gelatin zymography. (9) Test the influence of HB on B16 cells of C57BL/6 mice experimental pulmonary metastasis. (10) Test the influence of HB on H22 cells of mice experimental pulmonary metastasis. (11) Through establishing the purpose of using hamster cheek model induced by DMBA, observe cancerous pathological changes in six weeks, 9 weeks and 12 weeks to HB group and the modle group .Probe into the effect of HB on dimethyI-benzanthracene DMBA-induced buccal macosa premalignant lesion in hamsters.Results: HB acted synergistically with HCPT to significantly inhibit in vitro culture cells (SGC-7901,SW116,HepG2,SW480)proliferation. HB and 5–FU collaboratively could also inhibit those in vitro culture cells,and inhibit the growth of H22 and S180 solid tumors in mice. HB inhibited the activities of topoisomerase I and II. According to MTT method, different concentration of HB showed dose dependent inhibitory effects The results showed that HB could inhibit B16 cells from moving on Fibronection effectively by scratches experiments. After 48 h, the invasion of B16 cells was less than those in control groups, and the number of invasive cells was dose dependent. The activity levels of both MMP 2 and MMP 9 in B16 treated with HB were significantly low than control. To a certain extent, HB could influence murine established pulmonary metastases of H22 hepatoma and B16 melanoma .Compare to the modle group, the incidence of buccal lesion and cancer induced by DMBA in hamster was significantly lower in the group treated with HB in the dose of 54 and 72mg/kg.Conclusion: HB have synergistic action with 5-FU(in vivo and in vitro) or HCPT(in vitro) on suppressing tumor proliferation. HB can inhibit topoisomerase activity. HB can restrain the adhesion and sport ability of B16 cells on Fn, and inhibits B16 cells migrating ability in vitro. HB can inhibit lung metastasis of B16 melanoma and H22 hepatoma in mice. HB can inhibit the initiation and progression of buccal cancer induced by DMBA in hamster.