Abstract
The biochemical basis of multidrug-resistant (MDR) phenotype has been investigated in drug-resistant sublines independently obtained in our laboratories by single step doxorubicin (DOX) selection of LoVo, DLD1, and SW948 human colon carcinoma (HCC) cell lines. All the chemoresistant sublines have been found to be cross-resistant to DOX, actinomycin-D (ACT-D) and vincristine (VCR) but not to cis-diamminedichloroplatinum (CDDP), and have exhibited an increased expression level of mdr1 mRNA and gp170 glycoprotein. Comparative analyses in drug-resistant and sensitive cells of resistance index, extracellular and intracellular equitoxic DOX concentrations, and mdr1 gene products expression have indicated that MDR phenotype is a multifactorial phenomenon due to different and possibly independent biochemical mechanisms which cooperate, in varying degrees from cell line to cell line, in conferring cellular chemoresistance.
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- Chen C. J., Chin J. E., Ueda K., Clark D. P., Pastan I., Gottesman M. M., Roninson I. B. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381–389. doi: 10.1016/0092-8674(86)90595-7. [DOI] [PubMed] [Google Scholar]
- Chin J. E., Soffir R., Noonan K. E., Choi K., Roninson I. B. Structure and expression of the human MDR (P-glycoprotein) gene family. Mol Cell Biol. 1989 Sep;9(9):3808–3820. doi: 10.1128/mcb.9.9.3808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cole S. P., Downes H. F., Slovak M. L. Effect of calcium antagonists on the chemosensitivity of two multidrug-resistant human tumour cell lines which do not overexpress P-glycoprotein. Br J Cancer. 1989 Jan;59(1):42–46. doi: 10.1038/bjc.1989.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deffie A. M., Alam T., Seneviratne C., Beenken S. W., Batra J. K., Shea T. C., Henner W. D., Goldenberg G. J. Multifactorial resistance to adriamycin: relationship of DNA repair, glutathione transferase activity, drug efflux, and P-glycoprotein in cloned cell lines of adriamycin-sensitive and -resistant P388 leukemia. Cancer Res. 1988 Jul 1;48(13):3595–3602. [PubMed] [Google Scholar]
- Ferguson P. J., Fisher M. H., Stephenson J., Li D. H., Zhou B. S., Cheng Y. C. Combined modalities of resistance in etoposide-resistant human KB cell lines. Cancer Res. 1988 Nov 1;48(21):5956–5964. [PubMed] [Google Scholar]
- Gerlach J. H., Endicott J. A., Juranka P. F., Henderson G., Sarangi F., Deuchars K. L., Ling V. Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. Nature. 1986 Dec 4;324(6096):485–489. doi: 10.1038/324485a0. [DOI] [PubMed] [Google Scholar]
- Goldenberg G. J., Wang H., Blair G. W. Resistance to adriamycin: relationship of cytotoxicity to drug uptake and DNA single- and double-strand breakage in cloned cell lines of adriamycin-sensitive and -resistant P388 leukemia. Cancer Res. 1986 Jun;46(6):2978–2983. [PubMed] [Google Scholar]
- Hamada H., Tsuruo T. Functional role for the 170- to 180-kDa glycoprotein specific to drug-resistant tumor cells as revealed by monoclonal antibodies. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7785–7789. doi: 10.1073/pnas.83.20.7785. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kano T., Sakai M., Muramatsu M. Structure and expression of a human class pi glutathione S-transferase messenger RNA. Cancer Res. 1987 Nov 1;47(21):5626–5630. [PubMed] [Google Scholar]
- Kartner N., Riordan J. R., Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science. 1983 Sep 23;221(4617):1285–1288. doi: 10.1126/science.6137059. [DOI] [PubMed] [Google Scholar]
- Kaye S. B. The multidrug resistance phenotype. Br J Cancer. 1988 Dec;58(6):691–694. doi: 10.1038/bjc.1988.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ling V., Kartner N., Sudo T., Siminovitch L., Riordan J. R. Multidrug-resistance phenotype in Chinese hamster ovary cells. Cancer Treat Rep. 1983 Oct;67(10):869–874. [PubMed] [Google Scholar]
- Long B. H., Stringfellow D. A. Inhibitors of topoisomerase II: structure-activity relationships and mechanism of action of podophyllin congeners. Adv Enzyme Regul. 1988;27:223–256. doi: 10.1016/0065-2571(88)90019-2. [DOI] [PubMed] [Google Scholar]
- Lorico A., Toffoli G., Boiocchi M., Erba E., Broggini M., Rappa G., D'Incalci M. Accumulation of DNA strand breaks in cells exposed to methotrexate or N10-propargyl-5,8-dideazafolic acid. Cancer Res. 1988 Apr 15;48(8):2036–2041. [PubMed] [Google Scholar]
- Merkel D. E., Fuqua S. A., Tandon A. K., Hill S. M., Buzdar A. U., McGuire W. L. Electrophoretic analysis of 248 clinical breast cancer specimens for P-glycoprotein overexpression or gene amplification. J Clin Oncol. 1989 Aug;7(8):1129–1136. doi: 10.1200/JCO.1989.7.8.1129. [DOI] [PubMed] [Google Scholar]
- Pommier Y., Kerrigan D., Schwartz R. E., Swack J. A., McCurdy A. Altered DNA topoisomerase II activity in Chinese hamster cells resistant to topoisomerase II inhibitors. Cancer Res. 1986 Jun;46(6):3075–3081. [PubMed] [Google Scholar]
- Ponte P., Gunning P., Blau H., Kedes L. Human actin genes are single copy for alpha-skeletal and alpha-cardiac actin but multicopy for beta- and gamma-cytoskeletal genes: 3' untranslated regions are isotype specific but are conserved in evolution. Mol Cell Biol. 1983 Oct;3(10):1783–1791. doi: 10.1128/mcb.3.10.1783. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reeve J. G., Rabbitts P. H., Twentyman P. R. Amplification and expression of mdr1 gene in a multidrug resistant variant of small cell lung cancer cell line NCI-H69. Br J Cancer. 1989 Sep;60(3):339–342. doi: 10.1038/bjc.1989.282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riordan J. R., Deuchars K., Kartner N., Alon N., Trent J., Ling V. Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. 1985 Aug 29-Sep 4Nature. 316(6031):817–819. doi: 10.1038/316817a0. [DOI] [PubMed] [Google Scholar]
- Shen D. W., Fojo A., Chin J. E., Roninson I. B., Richert N., Pastan I., Gottesman M. M. Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification. Science. 1986 May 2;232(4750):643–645. doi: 10.1126/science.3457471. [DOI] [PubMed] [Google Scholar]
- Skovsgaard T. Mechanism of cross-resistance between vincristine and daunorubicin in Ehrlich ascites tumor cells. Cancer Res. 1978 Dec;38(12):4722–4727. [PubMed] [Google Scholar]
- Slovak M. L., Hoeltge G. A., Dalton W. S., Trent J. M. Pharmacological and biological evidence for differing mechanisms of doxorubicin resistance in two human tumor cell lines. Cancer Res. 1988 May 15;48(10):2793–2797. [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Toffoli G., Viel A., Bevilacqua C., Maestro R., Tumiotto L., Boiocchi M. In K562 leukemia cells treated with doxorubicin and hemin, a decrease in c-myc mRNA expression correlates with loss of self-renewal capability but not with erythroid differentiation. Leuk Res. 1989;13(4):279–287. doi: 10.1016/0145-2126(89)90064-7. [DOI] [PubMed] [Google Scholar]