Advertisement

Topics

MDR1 inhibition increases sensitivity to doxorubicin and etoposide in adrenocortical cancer.

07:00 EST 1st January 2019 | BioPortfolio

Summary of "MDR1 inhibition increases sensitivity to doxorubicin and etoposide in adrenocortical cancer."

Chemotherapy for adrenocortical carcinoma (ACC) has limited efficacy and is accompanied by severe toxicity. This lack of effectiveness has been associated with high tumoral levels of the multidrug resistance (MDR) pump P-glycoprotein (P-gp), encoded by the MDR1 gene. In this study, effects of P-gp inhibition on sensitivity of ACC cells to cytotoxic drugs were evaluated. MDR1 mRNA and P-gp expression were determined in human adrenal tissues and cell lines. H295R, HAC15, and SW13 cells were treated with mitotane, doxorubicin, etoposide, cisplatin, and streptozotocin, with or without the P-glycoprotein inhibitors verapamil and tariquidar. Cell growth and surviving fraction of colonies were assessed. MDR1 mRNA and P-gp protein expression were lower in ACCs compared to adrenocortical adenomas (P<0.0001; P<0.01, respectively). MDR1 and P-gp expression were positively correlated in ACC (P<0.0001, ρ = 0.723). Mitotane, doxorubicin, cisplatin, and etoposide dose-dependently inhibited cell growth in H295R, HAC15, and SW13. Tariquidar, and in H295R also verapamil, increased the response of HAC15 and H295R to doxorubicin (6.3 and 7.5 fold EC50 decrease in H295R, respectively; all P<0.0001). Sensitivity to etoposide was increased in H295R and HAC15 by verapamil and tariquidar (all P<0.0001). Findings were confirmed when assessing colony formation. We show that cytotoxic drugs, except streptozotocin, used for ACC treatment, inhibit ACC cell growth and colony formation at clinically achievable concentrations. P-gp inhibition increases sensitivity to doxorubicin and etoposide, suggesting that MDR1 is involved in sensitivity to these drugs and could be a potential target for cytotoxic treatment improvement in ACC.

Affiliation

Journal Details

This article was published in the following journal.

Name: Endocrine-related cancer
ISSN: 1479-6821
Pages:

Links

DeepDyve research library

PubMed Articles [21178 Associated PubMed Articles listed on BioPortfolio]

Advanced Adrenocortical Carcinoma - What to do when First-Line Therapy Fails?

Adrenocortical carcinoma is a rare endocrine malignant disease with a generally unfavorable but heterogeneous prognosis. Although even in advanced stages a subset of patients experiences long-term dis...

Efflux inhibition by HS confers sensitivity to doxorubicin-induced cell death in liver cancer cells.

Hydrogen sulfide (HS), an important gasotransmitter, is involved in a variety of cellular functions and pathophysiologic processes. Drug resistance due to alterations in drug trafficking and metabolis...

ETV7-Mediated DNAJC15 Repression Leads to Doxorubicin Resistance in Breast Cancer Cells.

Breast cancer treatment often includes Doxorubicin as adjuvant as well as neoadjuvant chemotherapy. Despite its cytotoxicity, cells can develop drug resistance to Doxorubicin. Uncovering pathways and ...

Inhibition of MALAT1 reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer.

Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA known to be highly expressed in several tumors. In colorectal cancer (CRC), MALAT1 promoted cell prolifer...

TIPE2 sensitizes osteosarcoma cells to cis-platin by down-regulating MDR1 via the TAK1- NF-κB and - AP-1 pathways.

TIPE2 participates in multiple types of cancer development. However, its mechanism underlying chemoresistance in osteosarcoma has not been elucidated. Herein, we observed the expression of TIPE2 and M...

Clinical Trials [13036 Associated Clinical Trials listed on BioPortfolio]

International Study: Comparison of Two Treatments for Adrenocortical Cancer

Background: - There is no medical consensus about the best treatment for advanced adrenocortical cancer (ACC) that cannot successfully be treated with surgery alone. - I...

Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Participants With Stage I-III Adrenocortical Cancer With High Risk of Recurrence

This phase III trial studies how well mitotane alone works compared to mitotane with cisplatin and etoposide when given after surgery in treating participants with adrenocortical cancer th...

A Study of Combination Chemotherapy and Surgical Resection in the Treatment of Adrenocortical Carcinoma: Continuous Infusion Doxorubicin, Vincristine and Etoposide With Daily Mitotane Before and After Surgical Resection

Patients who have no response to preoperative chemotherapy and no residual disease following surgery on Regimen A are treated on Regimen B postoperatively. The following acronyms are used...

Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor

RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving mo...

Adjuvant Chemotherapy vs. Observation/Mitotane After Primary Surgical Resection of Localized Adrenocortical CarcInoma

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Despite complete resection of early-stage disease recurrence rates in ACC are very high (60%.70%). Patients with Ki67 ≥ 10% ...

Medical and Biotech [MESH] Definitions

A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.

A benign neoplasm of the ADRENAL CORTEX. It is characterized by a well-defined nodular lesion, usually less than 2.5 cm. Most adrenocortical adenomas are nonfunctional. The functional ones are yellow and contain LIPIDS. Depending on the cell type or cortical zone involved, they may produce ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and/or ANDROSTENEDIONE.

A malignant neoplasm of the ADRENAL CORTEX. Adrenocortical carcinomas are unencapsulated anaplastic (ANAPLASIA) masses sometimes exceeding 20 cm or 200 g. They are more likely to be functional than nonfunctional, and produce ADRENAL CORTEX HORMONES that may result in hypercortisolism (CUSHING SYNDROME); HYPERALDOSTERONISM; and/or VIRILISM.

Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.

An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...


Searches Linking to this Article