Different sensitivities of human esophageal cancer cells to multiple anti-cancer agents and related mechanisms.
Mechanisms responsible for drug resistance in human esophageal cancer cell lines were investigated. Three cell lines established from human esophageal carcinoma (TE-1, SH-1, and TH) showed different sensitivities to vindesine, vincristine, cisplatin (CDDP), etoposide (VP-16), and pepleomycin. Both SH-1 and TH cell lines were twofold to sevenfold more resistant to pepleomycin, vindesine, and vincristine than TE-1 was. SH-1 showed twofold more resistance to CDDP than either TE-1 or TH did, and TH and TE-1 showed a 3-fold or 1.5-fold more resistance, respectively, to VP-16 than SH-1 did. The accumulation of tritiated vincristine in SH-1 and TH was approximately 50% that in TE-1. Two multidrug resistance reversal agents, cepharanthine and a synthetic dihydropyridine analogue (NK-252; Nikken Chemicals, Saitama, Japan), potentiated the cytocidal actions of vindesine against SH-1, TH, and TE-1 cells, with no apparent expression of P-glycoprotein in the three cell lines. The glutathione S-transferase pi gene was expressed in all three cell lines. DNA topoisomerase II levels were lowest in TE-1, followed by SH-1 and TH, although the accumulation of tritiated VP-16 was less in both TH and SH-1 than in TE-1. Differential sensitivities to anti-cancer drugs appear to be mediated through pleiotropic mechanisms.
Department of Surgery I, Oita Medical University, Japan.
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Saito
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Hikita
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Kohno
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Sato
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Takano
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Kobayashi
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004351:Drug Resistance / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis; D012334:RNA, Neoplasm / Q000302:isolation & purification; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D014750:Vincristine / Q000494:pharmacology; D014751:Vindesine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D012334:RNA, Neoplasm; D014750:Vincristine; D005047:Etoposide; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II; D014751:Vindesine