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Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis.
- Source :
-
BMC Cancer . 6/28/2017, Vol. 17, p1-13. 13p. 5 Diagrams, 1 Chart, 4 Graphs. - Publication Year :
- 2017
-
Abstract
- <bold>Background: </bold>Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in China and is an exceptionally drug-resistant tumor with a 5-year survival rate less than 15%. Cisplatin is the most commonly used conventional chemotherapeutic drug for the treatment of ESCC, but some patients have a poor response to cisplatin-based chemotherapy. New strategies that could enhance chemosensitivity to cisplatin are needed.<bold>Methods: </bold>We used reverse transcription-RCR (RT-PCR), immunoblot, immunohistochemical (IHC) staining, anchorage-dependent and -independent growth assays, co-immunoprecipitation (Co-IP) assay, RNA interference and in vivo tumor growth assay to study the expression of MCL-1 in ESCCs and the response of ESCC cells to cisplatin.<bold>Results: </bold>The present study showed that MCL-1 expression was significantly increased in ESCC tissues compared to normal adjacent tissues and was associated with depth of invasion and lymph node metastasis. Knockdown of MCL-1 produced significant chemosensitization to cisplatin in association with caspase-3 activation and PARP cleavage in KYSE150 and KYSE510 cells. The selective MCL-1 inhibitor UMI-77 caused dissociation of MCL-1 from the proapoptotic protein BAX and BAK, and enhanced KYSE150 and KYSE510 cells to cisplatin-induced apoptosis accompanied by caspase-3 activation and PARP cleavage.<bold>Conclusions: </bold>The current study suggests that MCL-1 contributes to the development of ESCC and is a promising therapeutic target for chemosensitization of ESCC cells to cisplatin. This might provide a scientific basis for developing effective approaches to treat the subset of ESCCs patients with MCL-1 overexpression. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SQUAMOUS cell carcinoma
*CISPLATIN
*IMMUNOPRECIPITATION
*TUMOR growth
*LYMPH nodes
*METASTASIS
*PROTEIN metabolism
*ANIMAL experimentation
*ANTINEOPLASTIC agents
*APOPTOSIS
*CELL physiology
*ESOPHAGEAL tumors
*MICE
*PROTEINS
*CANCER cell culture
*PRECIPITIN tests
*CHEMICAL inhibitors
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 17
- Database :
- Academic Search Index
- Journal :
- BMC Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 123915143
- Full Text :
- https://doi.org/10.1186/s12885-017-3442-y