Reversal of multidrug resistance in vincristine-resistant human gastric cancer cell line SGC7901/VCR by LY980503

瞄准：调查 LY980503 的颠倒效果， benflumetol 衍生物，在上多在长春新碱(VCR ) 的药抵抗抵抗的人的胃的癌房间线 SGC7901/VCR。方法：一根人的胃的癌症房间线， SGC7901，和它的 VCR- 抵抗变体的房间， SGC7901/VCR，与 LY980503 和 /or doxorubicin (纪录影片) 被栽培。药在试管内的细胞毒性是由 MTT 方法的 assayed。基于流动 cytometric 技术，纪录影片的举起被测量联系纪录影片的吝啬的荧光紧张(MFI ) 在这些房间检测。结果：SGC7901/VCR 房间是对与 SGC7901 房间比较的纪录影片更抵抗的 23.5 次。在 2.0 mumol/L -10 mumol/L 的集中的 LY980503 没有明显的细胞毒性到 SGC7901 和 SGC7901/VCR 房间。在有在 2.0 ， 4.0 和 10 mumol/L 的集中的 LY980503 的同时的治疗以后，到 SGC7901/VCR 房间的纪录影片的 IC50 从 1.6 +/-减少了 0.12 mumol/L 到 0.55 +/- 0.024 ， 0.25 +/- 0.032 和 0.11 +/- 0.015 mumol/L ，分别地这样，由2.9褶层增加 DOX 敏感( P 【 0 。05 ) ， 6.4 褶层(P 【 0。01 ) 并且 14.5 褶层(P 【 0。01 ) 分别地。在纪录影片的举起学习，有 LY980503 的 SGC7901/VCR 房间的同时的孵化显著地增加了 DOX 在 SGC7901/VCR 房间的联系 MFI。没有如此的结果在父母 SGC7901 房间被发现。结论：在非细胞毒素的集中的 LY980503 能有效地由增加细胞内部的纪录影片累积围绕 SGC7901/VCR 房间的抵抗到纪录影片。

AIM： To investigate the reversal effect of LY980503, a benflumetol derivative, on multidrug resistance in vincristine （VCR） -resistant human gastric carcinoma cell line SGC7901/VCR. METHODS： Cells of a human gastric cancer cell line, SGC7901, and its VCR-resistant variant, SGC7901/VCR, were cultivated with LY980503 and/or doxorubicin （DOX）. The cytotoxicity of drugs in vitro was assayed by M-IF method. Based on the flow cytometric technology, the uptake of DOX was detected in these cells by measuring DOX -associated mean fluorescence intensity （MFI）. RESULTS： SGC7901/VCR cells were 23.5 times more resistant to DOX in comparison with 5GC7901 cells. LY980503 at the concentrations of 2.0 μmol/L -10 μmol/ L had no obvious cytotoxicity to SGC7901 and SGC7901/ VCR cells. After simultaneous treatment with LY980503 at the concentrations of 2.0, 4.0 and 10 μmol/L, the ICso of DOX to SGC7901/VCR cells decreased from 1.6 ± 0.12 μmol/L to 0.55 ± 0.024, 0.25 ± 0.032 and 0.11 ± 0.015 μmol/L, respectively, thus, increasing the DOX sensitivity by 2.9-fold （P 〈 0. 05）, 6.4-fold （P 〈 0. 01） and 14.5-fold （P 〈 0. 01）, respectively. In the uptake study of DOX, simultaneous incubation of SGC7901/VCR cells with LY980503 significantly increased the DOX -associated MFI in SGC7901/VCR cells. No such results were found in parental SGC7901 cells. CONCLUSION： LY980503 at non-cytotoxic concentrations can effectively circumvent resistance of SGC7901/VCR cells to DOX by increasing intracellular DOX accumulation.