Prevention and treatment of total flavonoids from Gleditsiae Spina on lung cancer and its mechanisms / 中草药

ABSTRACT

Objective: To explore the prevention and treatment of total flavonoids from Gleditsiae Spina (TFGS) on lung cancer and its mechanisms. Methods: Mouse Lewis lung cancer (LLC) and embryonic lung fibroblast (L929) cells were treated with different doses of TFGS for 48 h, cell proliferation and adhesion were examined by MTT assay, and gap junctional intercellual communication (GJIC) was measured through scrape loading and dye transfer. The mice were randomly divided into model, quercetin (100 mg/kg, positive control), high-and low-dose (100 and 30 mg/kg) TFGS groups. The mice were ip injected with urethane twice weekly for five weeks to induce lung carcinogenesis and treated once daily for 10 weeks following the first urethane injection. The prevention of TFGS on chemocarcinogenesis was evaluated and the expression of gap junctional protein connexin 43 (Cx43) in lung tissue with tumors was compared by immunohistochemistry. The LLC cells were injected into the lateral axilla and tail vein respectively to establish the LLC sc allograft and experimental lung metastasis. The tumor-inocubating mice were randomly divided into model, doxorubicin (5 mg/kg, positive control), high-and low-dose (same as above) TFGS groups. The mice received the treatment for three weeks following tumor inocubation, and the effects of TFGS on the tumor size, metastasis, and life span were evaluated. Results: TFGS inhibited LLC cell proliferation in a dose dependent manner but had no effect on L929 cell proliferation in vitro. TFGS with a little effect on cell proliferation decreased cell adhesion and promoted GJIC in a dose dependent manner in LLC cells but did not affect the L929 cell adhesion. TFGS was able to prevent carcinogenesis induced by urethane and enhance Cx43 staining in lung region with tumor in immunohistochemistry. Compared with untreated model mice, GJIC reduced the tumor size and metastasis and prolongated life span in a dose dependent manner. Conclusion: TFGS could promote GJIC to prevent and treat tumor and might be a potential antitumor agent.