Reversal effect of TTD on human multidrug resistant KBV200 cell line.
The reversal effect of TTD (a Chinese medicine) on human multidrug- resistant KBV200 cell line was studied and compared with verapamil (VPL). The chemosensitivity of KBV200 was detected by MTT assay in vitro and the level of MDR1 mRNA of KBV200 was investigated by RT-PCR. The cytotoxicity of TTD to KBV200 and the parent sensitive cell line KB is very low and nearly same with a concentration of 10(-6) mol x L(-1). With the concentration TTD increased VCR cytotoxicity on KBV200, 50% inhibitory concentration (IC50) decreased from 1122.5+/-72.36 mol x L(-1) to 31.76+/-5.4 nmol x L(-1) (p<0.001). It was more effective than VPL was (p<0.01). The combination of low concentration of TTD (10(-8) mol x L(-1)) and VCR (100 nmol x L(-1)) has significantly increased VCR cytotoxicity on KBV200, cell Surviving Fraction decreased from 0.91+/-0.056 to 0.74+/-0.07 (p<0.02). TTD did not inhibit the expression of MDR1 mRNA of KBV200 with the concentration of 10(-6) mol x L(-1). These data indicated that TTD could reverse VCR resistance of KBV200 and may be useful in enhancing the clinical effectiveness of VCR.
Xu
J Y
JY
Central Laboratory, Chongqing Cancer Institute, P R China.
Zhou
Q
Q
Shen
P
P
Tang
W
W
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000470:Alkaloids / Q000633:toxicity*; D044182:Benzylisoquinolines; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D006801:Humans; D007624:KB Cells; D008516:Medicine, Chinese Traditional; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014700:Verapamil / Q000494:pharmacology*; D014750:Vincristine / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D044182:Benzylisoquinolines; D012333:RNA, Messenger; C009438:tetrandrine; D014750:Vincristine; D014700:Verapamil