• 1.華西醫(yī)科大學附屬第一醫(yī)院普外科（成都610041）;;
  • 2.華西醫(yī)科大學法醫(yī)學院物證教研室;;
  • 3.華西醫(yī)科大學腫瘤研究所;;
  • 4.華西醫(yī)科大學附屬第一醫(yī)院生物治療中心。;

目的  觀察反義硫代磷酸寡核苷酸（ASOND）逆轉耐藥肝癌細胞的多藥耐藥作用。
方法  用人工合成互補于mdrl基因5′端AUG起始密碼子的反義20聚硫代磷酸寡核苷酸，以Lipofectamine為載體，轉染人耐藥肝癌細胞SMMC-7721，MTT測定細胞對化療藥物的敏感性，通過RT-PCR檢測mRNA的表達，流式細胞儀分析P-170的表達。
結果  ASOND可抑制SMMC-7721細胞mRNA及P-170的表達，增加耐藥細胞對化療藥物的敏感性，最佳ASOND作用濃度為0.5μmol/L。
結論  ASOND可增加耐藥細胞對化療藥物的敏感性，部分逆轉耐藥肝癌細胞耐藥。

引用本文： 羅華友,楊家印,林琦遠,嚴律南,黃代新,張潔,雷松,趙永恒. 反義硫代磷酸寡核苷酸逆轉肝癌細胞多藥耐藥的實驗研究. 中國普外基礎與臨床雜志, 2001, 8(4): 220-222. doi: 復制

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6. Behr JP, Demeneix B, Loeffler JP, et al. Efficient gene transfer into mammalian primary endocrine cells with lipopolyaminecoated DNA 〔Ｊ〕. Proc Natl Acad Sci USA, 1989; 86(18)∶6982.
7. Wagner RW. Gene inhibition using antisense oligodeoxynuxleotides 〔Ｊ〕. Nature, 1994; 372(6504)∶333.
8. Richert ND, Laldwin D, Nilescki MM, et al. Stability and covalent modification of Pglycoprotein in multidrug resistance KB cells 〔Ｊ〕. Biochemistry, 1988; 27(20)∶7607.
9. Walder RY, Walder JA. Role of Rnase H in hybridarrested translation by antisense oligonucleotides 〔Ｊ〕. Proc Natl Acad Sci USA, 1988; 85(14)∶5011.
10. Kulka M, Simith CC, Aurelian R, et al. Site specificity of the inhibitory effects of oligo (nucleotide methylphonate)s complementary to the acceptor splice junction of herpes simplex virus type1 immediate early mRNA 〔Ｊ〕. Proc Natl Acad Sci USA, 1989; 86(18)∶6868.
11. Boiziau C, Kurfurst C, Cazenave V, et al. Inhibition of translation initiation by antisense oligonucleotides via an RnaseH independent mechanism 〔Ｊ〕. Nucleic Acids Res, 1991; 19(5)∶1113.
  1. 1. Christensen JG, LeBlanc GA. Reversal of multidrug resistance in vivo by dietary administration of the photochemical indole3carbinol 〔Ｊ〕. Cancer Res, 1996; 56(3)∶574.
  2. 2. Alahari SK, Dean MH, Fisher R, et al. Inhition of expression of the multidrug resistance associated Pglycoprotein by phosphorothioate and 5′cholesterolconjugated phosphorothioate antisense oligonucleotides 〔Ｊ〕. Molecular Pharmacology, 1996; 50(4)∶808.
  3. 3. Noonan KE, Beck C, Holzmayer TA, et al. Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction 〔Ｊ〕. Proc Natl Acad Sci USA, 1990; 87(18)∶7160.
  4. 4. Sargent JM, Taylor CG. Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeioid lekaemia 〔Ｊ〕. Br J Cancer, 1989; 60(2)∶206.
  5. 5. Roninson IB. The role of MDR1(Pglycoprotein) gene in multidrug resistance in vitro and in vivo 〔Ｊ〕. Biochem Pharmacol, 1992; 43(1)∶95.
  6. 6. Behr JP, Demeneix B, Loeffler JP, et al. Efficient gene transfer into mammalian primary endocrine cells with lipopolyaminecoated DNA 〔Ｊ〕. Proc Natl Acad Sci USA, 1989; 86(18)∶6982.
  7. 7. Wagner RW. Gene inhibition using antisense oligodeoxynuxleotides 〔Ｊ〕. Nature, 1994; 372(6504)∶333.
  8. 8. Richert ND, Laldwin D, Nilescki MM, et al. Stability and covalent modification of Pglycoprotein in multidrug resistance KB cells 〔Ｊ〕. Biochemistry, 1988; 27(20)∶7607.
  9. 9. Walder RY, Walder JA. Role of Rnase H in hybridarrested translation by antisense oligonucleotides 〔Ｊ〕. Proc Natl Acad Sci USA, 1988; 85(14)∶5011.
  10. 10. Kulka M, Simith CC, Aurelian R, et al. Site specificity of the inhibitory effects of oligo (nucleotide methylphonate)s complementary to the acceptor splice junction of herpes simplex virus type1 immediate early mRNA 〔Ｊ〕. Proc Natl Acad Sci USA, 1989; 86(18)∶6868.
  11. 11. Boiziau C, Kurfurst C, Cazenave V, et al. Inhibition of translation initiation by antisense oligonucleotides via an RnaseH independent mechanism 〔Ｊ〕. Nucleic Acids Res, 1991; 19(5)∶1113.