关键词: 丹酚酸A, 抗肿瘤, 多药耐药, 半数抑制浓度

Abstract:

AIM: To explore the anti-tumor effect of salvianolic acid A(SAA) and to research its reversal effect of multidrug resistance on A549/MTX tumor. METHODS: The human lung carcinoma cell line A549 and human lung carcinoma drug-resisitant cell line A549/MTX were cultured in vitro and were divided into three groups: blank control group (medium only), negative control group (cell suspension plus medium) and experimental group (cell suspension plus three kinds of ant-tumor drugs). SAA in five concentrations (4, 8, 16, 32, and 64 μg/mL) intervened A549 cells. The inhibition effects of SAA of 4, 8, 16, 32, and 64 μg/mL in 24 h, 48 h and 48 h on A549 cell proliferation were tested by MTT assay. The IC₅₀ of MTX，CDDP，and GEF for the cell of A549，A549/MTX were determined by MTT assay. The IC₅₀ of MTX，CDDP，and GEF for the A549/MTX after intervention with SAA were determined also by MTT assay. The sensitivity change and drug reversal effect of SAA before and after intervention on the A549/MTX cell line were investigated by MTT assay. RESULTS: The inhibition rate after intervention with SAA on A549 cells for 24 h was increased from (9.16±3.64)% (4 μg/mL) to (52.93±5.21)% (64 μg/mL). Accordingly, the inhibition rate of SAA were (54.93±5.21)%, (63.83±2.74)%, (72.91±4.06)% for 24 h, 48 h and 72 h as the concentration was increased to 64 μg/mL. Anti-proliferative effects of SAA on A549 cells were significant, and the inhibition rate increased with dose dependence and time dependence. Inhibition rate of SAA of 4 μg/mL on A549 and A549/MTX cell growth were 9.16% and 7.38%, respectively. Both less than 10% and no obvious toxic effect was observed, so concentration of 4 μg/mL was choosed as safety experiment dose for lung cancer drug resistant. When 4 μg/mL SAA intervened on A549/MTX cell, MTX to A549/MTX half inhibitory concentration was from (105.72±4.62) μg/mL to (26.13±1.36) μg/mL. Reverse ratio was 4.05. Half inhibitory concentration of CDDP on A549/MTX cell was from (174.92±6.86) μg/mL to (49.89±1.73) μg/mL, reverse ratio was 3.51. Half inhibitory concentration of GEF on A549/MTX cell was from (251.38±8.64) μg/mL to (116.93±5.22) μg/mL, reverse ratio was 2.15. Compared with the effect on A549 cells，MTX, CDDP, and GEF presented significant difference (P<0.01). Compared with the effect on A549/MTX cell intervened with SAA，MTX, CDDP, and GEF presented significant effect on A549/MTX cells (P<0.01). CONCLUSION: SAA can inhibit the growth of A549 cells and A549/MTX cells, and partially reverse the multidrug resistance of A549/MTX in vitro．

Key words: salvianolic acid A (SAA), anti-tumor, multi-resistant, half maximal inhibitory concentration