Objective To investigate the reversal of the multidrug resistant gene mdr1 in vivo by antisense oligodeoxynucleotide （ASODN） on the basis of study in vitro. Methods The cultured drug-resistant human hepatocellular carcinoma cells were injected under the skin of axilla to establish the tumor model of nude mice. mdr1 ASODN accompanied by Lipofectamine were injected locally and ADM was injected intraperitoneally. Control 1 and control 2 were locally injected by Lipofectamine and normal saline separately, and ADM was also injected intraperitoneally. Results As time went on the tumor size increased and from the 5th day on alterations were marked, tumor size in different time phase showed marked difference to the prior time phase with significant difference (P＜0.05）. Tumor size in group ASODN was marked smaller than that of other 3 groups after the 5th day (P＜0.05)，while tumor size of group control 1,2 and group SODN in different phase showed no significant difference (Pgt;0.05). The results suggested that SODN and Lipofectamine showed no marked effect on tumor growth of nude mice and ASODN had marked inhibition effect on tumor growth. Conclusion mdr1 ASODN can also reverse multidrug resistance of drug-resistant human hepatocellular carcinoma cells in vivo. After the treatment the tumor’s growth in nude mice will slow down in a range of time.
Objective To investigate the reversal effect of antisense phosphorothioate oligonucleotide （ASOND) on human hepatoma resistant cells. Methods Human hepatoma resistant cells SMMC-7721 was transfected with synthetic antisense phosphorothioate oligonucleotide complementary to the 5′ region flanking the AUG initiation codon mediated by lipofectamine. In vitro drug sensitivity was measured by MTT assay. The expression of P-170 was determined by flow cytometry and mRNA was assessed by RT-PCR. Results ASOND inhibited the expression of mRNA and p-170 in SMMC-7721, enhanced the sensitivity of SMMC-7721 to chemotherapeutic drug. The best inhibitory effect was achived by the dose of 0.5μmol/L. Conclusion ASOND enhanced the sensitivity of SMMC-7721 to chemotherapeutic drug and reversed the multidrug resistance of SMMC-7721 partially.