Multidrug Resistance and P-Glycoprotein Expression

Ling, Victor; Juranka, Peter F.; Endicott, J.A.; Deuchars, Kathryn L.; Gerlach, James H.

doi:10.1016/b978-0-12-763362-6.50020-0

Cited by 19 publications

(14 citation statements)

References 39 publications

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“…For resistance mechanisms, the qualitative and quantitative alteration of the target enzyme of chemotherapeutic drugs, for example topoisomerase, alteration of glutathione metabolism and the alteration of genes pertinent apoptosis have been reported [16,20,21]. As the mechanisms are different depending on the cancer type and type of chemotherapeutic drug, it is important to characterize resistance mechanisms accurately.…”

Section: Discussionmentioning

confidence: 99%

Effect of Betulinic Acid on Anticancer Drug‐Resistant Colon Cancer Cells

Jung¹,

Kim²,

Choi³

et al. 2007

Basic Clin Pharma Tox

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Primary or acquired resistance of tumours to established chemotherapeutic regimens is a major concern in oncology. Attempts to improve the survival of cancer patients largely depend on strategies to prevent tumour cell resistance. 5-Fluorouracil (5-FU)-based chemotherapy with a combination of other drugs such as irinotecan (IRT) and oxaliplatin (OXT) has been reported to be effective, even though an optimal regimen has yet to be defined due to the relatively high toxicity of the procedure. The aim of this study was to examine the effect of betulinic acid (BetA) as a chemosensitizer for anticancer drug treatment in chemoresistant colon cancer cell lines. A chemoresistant cell line to 5-fluorouracil (SNU-C5/ 5FU-R), irinotecan (SNU-C5/IRT-R) and oxaliplatin (SNU-C5/OXT-R) treatment were derived from the wild-type colon adenocarcinoma cell line (SNU-C5/WT). The effect of BetA or a combination of anticancer drugs and BetA on the multidrug resistance-related genes, caspases, Bcl-2, Bad and cell death in the SNU-C5/WT and SNU-C5/R cell lines was analysed. BetA alone was an effective chemotherapeutic drug for the SNU-C5/WT, SNU-C5/5FU-R and SNU-C5/OXT-R cells. The combination of BetA with IRT or OXT was effective against SNU-C5/5FU-R cells, and the combination of BetA with 5-fluorouracil, IRT or OXT was effective against SNU-C5/OXT-R cells. BetA induced cancer cell death by apoptosis through the mitochondrial pathway. These findings indicate that the use of BetA as a chemosensitizer may be a new strategy to enhance the efficacy of chemotherapy. However, further studies will be needed for confirmation.The incidence of colorectal cancer is 8.5% of all cancers and may be related to lifestyle, obesity, drinking, smoking and other factors. The cancer death rate due to colorectal cancer remains high [1]. Although the complete remission of colorectal cancer is possible by surgical removal, unfortunately, approximately 50% of cases eventually develop incurable metastatic disease despite adjuvant treatment [2].5-Fluorouracil (5-FU)-based chemotherapy has been used as a basic treatment protocol to prolong the survival of metastatic colorectal cancer patients and improve their quality of life [3]. However, the response rate of metastatic colorectal cancer to 5-FU is approximately 20%. Recently, aggressive treatments containing new drugs such as irinotecan (IRT) or oxaliplatin (OXT) have been utilized in place of traditional treatments solely using fluoropyrimidines [4]. IRT is a semisynthetic derivative of camptothecin that suppresses topoisomerase I. The response rate is approximately 15%, and troublesome diarrhoea may develop. Recently, to increase its efficacy, combination therapy with 5-FU and leucovorin has been used. The action mechanism of OXT is similar to that of cisplatin, carboplatin or other platinum derivatives, and within tumour cells they form a cross-link with DNA resulting in the suppression of DNA replication and RNA transcription [5]. Recently, colorectal cancer patients who failed 5-FU treatment have...

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Section: Discussionmentioning

confidence: 99%

Effect of Betulinic Acid on Anticancer Drug‐Resistant Colon Cancer Cells

Jung¹,

Kim²,

Choi³

et al. 2007

Basic Clin Pharma Tox

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“…Multidrug resistance (MDR) is a complex phenotype involving resistance to a variety of unrelated low MW drugs. A wide variety of biochemical changes have been detected in MDR cell lines (LING 1987). The most constant alteration found is the overexpression of the P-glycoprotein and gene amplification (RIORDAN and LING 1985).…”

Section: Multidmg Resistancementioning

confidence: 99%

Soluble Polymers as Targetable Drug Carriers

Krinick¹,

Kopeček²

1991

Targeted Drug Delivery

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“…Proteins involved in MDR mechanisms are P-glycoprotein (P-gp), MDR-associated proteins, major vault protein/lung resistance-related protein, and breast cancer resistance protein [1,2]. One form of MDR is caused by overexpression of P-gp, the MDR1 gene product [3,4]. Overexpression of P-gp confers cancer cell resistance to a variety of chemotherapeutic drugs and constitutes one of the major obstacles to successful treatment of numerous types of malignancies.…”

Section: Introductionmentioning

confidence: 99%

Involvement of MyoD and PEA3 in regulation of transcription activity of MDR1 gene

Zhao¹,

Liu²,

Qi³

et al. 2010

ABBS

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Overexpression of multidrug resistance 1 (MDR1) in cancer remains one of the major causes for the failure of chemotherapy. In the present study, we found that MyoD and PEA3 could activate P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of MyoD and PEA3 attenuated MDR1 expression and increased the sensitivity of multidrug resistant cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. MyoD or PEA3 could bind to the E-box and PEA3 sites on the MDR1 promoter and activate its transcription. The regulation of MDR1 expression by MyoD and PEA3 may provide potential ways to overcome MDR in cancer treatment.

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Multidrug Resistance and P-Glycoprotein Expression

Cited by 19 publications

References 39 publications

Effect of Betulinic Acid on Anticancer Drug‐Resistant Colon Cancer Cells

Effect of Betulinic Acid on Anticancer Drug‐Resistant Colon Cancer Cells

Soluble Polymers as Targetable Drug Carriers

Involvement of MyoD and PEA3 in regulation of transcription activity of MDR1 gene

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