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Updated: Jun 1, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Roles of sildenafil in enhancing drug sensitivity in cancer
Zhi Shi1, Amit K Tiwari, Atish S Patel
1Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Queens, New York, USA.
Abstract:
The phenomenon of multidrug resistance (MDR) has decreased the hope for successful cancer chemotherapy. The ATP-binding cassette (ABC) transporter superfamily is the largest transmembrane family. The overexpression of ABC transporters is a major determinant of MDR in cancer cells both in vitro and in vivo. Unfortunately, until recently, most of the strategies used to surmount ABC-transporter-mediated MDR have had limited success. An ideal modulator of MDR would be one that has a low liability to induce toxicity and alter the pharmacokinetic profile of antineoplastic drugs. Sildenafil, an inhibitor of cGMP-specific phosphodiesterase type 5, was found to significantly reverse ABC-transporter-mediated MDR. Our results indicate that sildenafil has differential inhibitory effects on ABC transporters: It significantly decreases the efflux activity of ABCB1 and ABCG2, but has no significant effects on ABCC1. Emerging evidence indicates that sildenafil and other phosphodiesterase type 5 inhibitors may enhance the sensitivity of certain types of cancer to standard chemotherapeutic drugs.
Insights
Sildenafil reverses multidrug resistance (MDR) in cancer by inhibiting ATP-binding cassette (ABC) transporters like ABCB1 and ABCG2. This finding offers new hope for enhancing chemotherapy effectiveness against resistant tumors.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Multidrug resistance (MDR) significantly limits the efficacy of cancer chemotherapy.
- Overexpression of ATP-binding cassette (ABC) transporters is a primary driver of MDR in cancer cells.
- Current strategies to overcome ABC transporter-mediated MDR have shown limited success.
Purpose of the Study:
- To investigate the potential of sildenafil, a phosphodiesterase type 5 inhibitor, to reverse ABC transporter-mediated MDR.
- To determine the differential effects of sildenafil on various ABC transporters.
- To explore sildenafil's potential role in enhancing cancer chemotherapy sensitivity.
Main Methods:
- Utilized sildenafil as an inhibitor of cGMP-specific phosphodiesterase type 5.
- Assessed the impact of sildenafil on the efflux activity of key ABC transporters, including ABCB1, ABCG2, and ABCC1.
- Evaluated the reversal of MDR in cancer cells in vitro and in vivo.
Main Results:
- Sildenafil was found to significantly reverse ABC transporter-mediated MDR.
- Sildenafil demonstrated differential inhibitory effects, significantly decreasing efflux activity for ABCB1 and ABCG2.
- No significant effect of sildenafil was observed on ABCC1 efflux activity.
Conclusions:
- Sildenafil effectively reverses MDR mediated by specific ABC transporters (ABCB1, ABCG2).
- Sildenafil exhibits a selective inhibitory profile against ABC transporters.
- Sildenafil and related phosphodiesterase type 5 inhibitors represent a promising strategy to enhance cancer chemotherapy sensitivity.
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