The Mechanism of Acquired Resistance to Cisplatin by a Human Ovarian Cancer Cell Line

Kikuchi, Yoshihiro; Iwano, Ichiro; Miyauchi, Munenori; Kita, Toru; Oomori, Keibun; Kizawa, Isao; Sugita, Michio; Tenjin, Y

doi:10.1111/j.1349-7006.1988.tb00033.x

Cited by 18 publications

(11 citation statements)

References 9 publications

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“…For this purpose, we used CDDPresistant ovarian cancer cell line, KFr13 cells, established from KF28 cells derived from human serous cystadenocarcinoma of the ovary. 23 The IC50 of CDDP was compared among KF28, KFr13 and SKOV3 cells and is shown in Figure 3a. KFr13 cells exhibited much higher IC50 than KF28 or SKOV3 cells, as expected.…”

Section: Resultsmentioning

confidence: 99%

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Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affects survival in a xenograft model with peritoneal dissemination

et al. 2009

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Despite tremendous development in chemotherapy for ovarian cancer over the past few decades, the prognosis of advanced cases with massive peritoneal dissemination is still unsatisfactory, and novel treatment modalities that can combine with chemotherapy are urgently needed. We recently developed virotherapy for solid tumors using telomerase-specific replication-selective adenoviruses (Telomelysin: OBP-301), in which the human telomerase reverse transcriptase (hTERT) gene promoter has been inserted to direct tumor-specific E1 gene expression. In this study, we investigated the anti-tumor effects of OBP-301, combined with cisplatin (CDDP), on ovarian cancer cells. In vitro treatment of SKOV3 cells with OBP-301 at a multiplicity of infection (MOI) of 0.01-100 induced significant cell death in a dose-dependent manner, with moderate cytotoxicity at an MOI of 1-10 and maximal cytotoxicity at an MOI of 100. In contrast, OBP-301 treatment of normal human cells showed no significant cell death at an MOI of 1-10 and exhibited modest cytotoxicity at an MOI of 100. The effects of low-dose CDDP at 0.5-1 mM, which induced only 20% cell death, were significantly augmented by combination with OBP-301 at an MOI of 1-10, finally achieving 40% cell death. Such enhancement of CDDP sensitivity was also observed in CDDP-resistant ovarian cancer cells. The combinatorial effects were further tested using a xenograft mouse model of SKOV3 with peritoneal dissemination. After intraperitoneal administration of OBP-301, we confirmed that injected OBP-301 fused with the green fluorescent protein (GFP) gene (OBP-401) was preferentially localized to peritoneal disseminations, as determined by fluorescence imaging. Treatment of mice with CDDP at low dose (0.5 mg kg -1 ) had modest effects, showing a 10% decrease in disseminations, whereas combination with intraperitoneal administration of OBP-301 at an MOI of 10 led to enhanced effects, achieving an approximately 80% decrease in disseminations. Kaplan-Meier analysis showed improved overall survival of mice treated with CDDP plus OBP-301 compared with CDDP alone. These findings support the therapeutic potential of intraperitoneal administration of OBP-301 to sensitize ovarian cancer cells to CDDP.

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Section: Resultsmentioning

confidence: 99%

“…KF28 cells were derived from serous cystadenocarcinoma of the ovary, from which CDDP-resistant KFr13 cells were established. 23 Both cells were cultured in the above conditions.…”

Section: Cell Culturementioning

confidence: 99%

Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affects survival in a xenograft model with peritoneal dissemination

et al. 2009

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“…Cell Culture-Human ovarian cancer cell line HRA was grown and cultured as described previously (16). The HRA cells were maintained in RPMI 1640 medium supplemented with 10% FBS in a cell culture incubator (constantly set at 37°C with 5% CO 2 ).…”

Section: Methodsmentioning

confidence: 99%

Transforming Growth Factor-β1 Produced by Ovarian Cancer Cell Line HRA Stimulates Attachment and Invasion through an Up-regulation of Plasminogen Activator Inhibitor Type-1 in Human Peritoneal Mesothelial Cells

Hirashima

Kobayashi

Suzuki

et al. 2003

Journal of Biological Chemistry

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The processes of ovarian cancer dissemination are characterized by altered local proteolysis, cellular proliferation, cell attachment, and invasion, suggesting that the urokinase-type plasminogen activator (uPA) and its specific inhibitor (plasminogen activator inhibitor type-1 (PAI-1)) could be involved in the pathogenesis of peritoneal dissemination. We showed previously that expression of uPA and PAI-1 in the human ovarian cancer cell line HRA can be down-regulated by exogenous bikunin (bik), a Kunitz-type protease inhibitor, via suppression of transforming growth factor-␤1 (TGF-␤1) up-regulation and that overexpression of the bik gene can specifically suppress the in vivo growth and peritoneal dissemination of HRA cells in an animal model. We hypothesize that the plasminogen activator system in mesothelial cells can be modulated by HRA cells. To test this hypothesis, we used complementary techniques in mesothelial cells to determine whether uPA and PAI-1 expression are altered by exposure to culture media conditioned by HRA cells. Here we show the following: 1) that expression of PAI-1, but not uPA, was markedly induced by culture media conditioned by wild-type HRA cells but not by bik transfected clones; 2) that by antibody neutralization the effect appeared to be mediated by HRA cell-derived TGF-␤1; 3) that exogenous TGF-␤1 specifically enhanced PAI-1 up-regulation at the mRNA and protein level in mesothelial cells in a timeand concentration-dependent manner, mainly through MAPK-dependent activation mechanism; and 4) that mesothelial cell-derived PAI-1 may promote tumor invasion possibly by enhancing cell-cell interaction. This represents a novel pathway by which tumor cells can regulate the plasminogen activator system-dependent cellular responses in mesothelial cells that may contribute to formation of peritoneal dissemination of ovarian cancer.

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“…Teicher et al (1986) reported that a CDDPresistant head and neck squamous cell carcinoma cell line (SCC-25/CP) showed cross-resistance to methotrexate, but not to FUra. In addition, Kikuchi et al (1988) reported that a CDDP-resistant cell line, KFr, derived from human serous cystadenocarcinoma of the ovary, showed no cross-resistance to FUra. Accordingly, the determinants relating to the sensitivity or resistance to FUra in CDDP-resistant cell lines might differ with the cell line.…”

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confidence: 99%

Mechanisms of collateral sensitivity to fluorouracil of a cis-diamminedichloroplatinum(II)-resistant human non-small lung cancer cell line

Sugimoto¹,

Ohe²,

Nishio³

et al. 1992

Br J Cancer

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A cisplatin(CDDP)-resistant subline of a human lung cancer cell line, PC-7/CDDP, was 4.7-fold more resistant to CDDP than the parent line in a colony-forming assay. The sensitivity of this cell line to anthracyclines, vinca-alkaloid, etoposide, mitomycin C, and bleomycin was similar to that of the parental line, PC-7. However, PC-7/CDDP exhibited 4-fold higher sensitivity to fluorouracil (FUra). Possible mechanisms associated with the collateral sensitivity to FUra were studied in PC-7/CDDP cells. The sensitivity of both cell lines to FUra did not correlate with the effect of FUra on RNA. On the other hand, FUra induced a greater reduction in dTTP pools and more single strand breaks in PC-7/CDDP than in PC-7 cells. These results suggest that the pathway for de novo deoxyribonucleotide synthesis may be a target for FUra in PC-7/CDDP cells. However, inhibition of thymidylate synthase after FUra treatment did not correlate with the DNA-directed activity of FUra. Based on the above findings, the decreased salvage synthesis of dTTP was considered a possible mechanism of the greater reduction of dTTP pools in PC-7/CDDP cells. However, the activity of dThd kinase was the same in both cell lines. In the presence of physiological concentrations of exogenous dThd in the serum, uptake of dThd was less in PC-7/CDDP cells than that in PC-7 cells. Our data suggest that FUra-induced cytotoxicity in PC-7/CDDP cells is associated with the inhibition of dTTP synthesis and that the decreased uptake of dThd is a possible mechanism of the collateral sensitivity to FUra in PC-7/CDDP cells.

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The Mechanism of Acquired Resistance to Cisplatin by a Human Ovarian Cancer Cell Line

Cited by 18 publications

References 9 publications

Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affects survival in a xenograft model with peritoneal dissemination

Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affects survival in a xenograft model with peritoneal dissemination

Transforming Growth Factor-β1 Produced by Ovarian Cancer Cell Line HRA Stimulates Attachment and Invasion through an Up-regulation of Plasminogen Activator Inhibitor Type-1 in Human Peritoneal Mesothelial Cells

Mechanisms of collateral sensitivity to fluorouracil of a cis-diamminedichloroplatinum(II)-resistant human non-small lung cancer cell line

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