Clinically relevant concentrations of verapamil do not enhance the sensitivity of human bone marrow CFU-GM to adriamycin and VP16

Ma, Smith; Merry, Stephen; Jg, Smith; Kaye, SB

doi:10.1038/bjc.1988.131

Cited by 8 publications

(1 citation statement)

References 14 publications

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“…Previously, VER has been reported to reverse multidrug resistance ( 26 , 27 ). Consistent with this, the present study demonstrated that VER significantly increased the efflux of R123, indicating that VER increases the quantity of soluble intercellular agents by inhibiting the function of Pgp, thus increasing the efficiency of chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance

Wang

2014

Oncology Letters

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The aim of the present study was to investigate the underlying mechanisms of methotrexate (MTX) resistance in the human osteosarcoma cell line, Saos-2/MTX4.4, and to evaluate various methods of overcoming the resistance to this chemotherapeutic agent. MMT assays were performed to determine the resistance of the primary (Saos-2) and resistant (Saos-2/MTX4.4) cell lines to MTX, cisplatin [cis-diamminedichloroplatinum II (DDP)], ifosfamide (IFO), Adriamycin (ADM), epirubicin (EPI) and theprubicin (THP). The Saos-2/MTX4.4 cells exhibited a low resistance to IFO, ADM, EPI and THP; however, no resistance to DDP was identified. Overall, the Saos-2/MTX4.4 cells exhibited a greater resistance to all the chemotherapeutic agents investigated compared with the Saos-2 cells. Rhodamine 123 (R123) fluorescence was measured in the Saos-2/MTX4.4 and Saos-2 cells 30 and 60 min after the addition of R123, and R123 plus verapamil (VER). VER administration increased the intracellular accumulation of R123. In addition, reverse transcription-quantitative polymerase chain reaction was performed to determine the mRNA expression levels of multidrug resistance gene 1 (MDR1) in the two cell lines. Although the Saos-2/MTX4.4 cells were more resistant to the chemotherapeutic agents than the Saos-2 cells, no significant difference was identified between the relative mRNA expression levels of MDR1 in the Saos-2/MTX4.4 and Saos-2 cells (0.4350±0.0354 vs. 0.3886±0.0456; P>0.05).

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Section: Discussionmentioning

confidence: 99%

Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance

Wang

2014

Oncology Letters

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Enhancement of cytotoxicity of doxorubicin by verapamil in the hepatic artery infusion for liver tumors in rats

Miyazaki

Shimoda

Itoh

et al. 1993

Cancer

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Background. The calcium channel blocker has been demonstrated to be effective in the accumulation and retention of chemotherapeutic agents in tumor cells. Methods. The effect of verapamil on cytotoxicity of doxorubicin was investigated in a hepatic artery infusion (HAI) for liver tumors of Walker 256 carcinosarcoma in rats. Doxorubicin was infused by way of a hepatic artery by a bolus injection intra‐arterially (IA) (1 mg/kg) and a continuous infusion intra‐arterially (CIA) (6 mg/kg/day for 6 days). Results. Doxorubicin increased 90% and 66% in tumor tissue following HAI of verapamil by a bolus and continuous infusion (P < 0.05), respectively. However, no enhancement of the accumulation of doxorubicin in the tumor tissue was found in an intravenous administration of verapamil. The CIA infusion of verapamil with doxorubicin inhibited the tumor growth by 73% in comparison with doxorubicin only (P < 0.05). Verapamil administered intravenously (IV) could not induce this inhibitory effect. The CIA administration of verapamil reduced the serum concentration by 45% (P < 0.001) in comparison with the CIV route. Furthermore, the administration of verapamil did not increase the accumulation of doxorubicin in the normal liver and heart tissues. No enhancement of bone marrow suppression and hepatic biochemical influence by doxorubicin was revealed by the concomitant use of verapamil. Conclusions. The continuous HAI of verapamil remarkably enhanced the cytotoxicity of HAI with doxorubicin for the treatment of hepatic tumor without aggravating the side effects induced by doxorubicin.

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Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes

Oudard

Thierry

Jorgensen

et al. 1991

Cancer Chemother. Pharmacol.

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Clinically relevant concentrations of verapamil do not enhance the sensitivity of human bone marrow CFU-GM to adriamycin and VP16

Cited by 8 publications

References 14 publications

Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance

Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies for overcoming this resistance

Enhancement of cytotoxicity of doxorubicin by verapamil in the hepatic artery infusion for liver tumors in rats

Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes

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