Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis
Abstract Background 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...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3442-y |
| _version_ | 1811278008676253696 |
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| author | Xinfang Yu Wei Li Zhenkun Xia Li Xie Xiaolong Ma Qi Liang Lijun Liu Jian Wang Xinmin Zhou Yifeng Yang Haidan Liu |
| author_facet | Xinfang Yu Wei Li Zhenkun Xia Li Xie Xiaolong Ma Qi Liang Lijun Liu Jian Wang Xinmin Zhou Yifeng Yang Haidan Liu |
| author_sort | Xinfang Yu |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-04-13T00:27:01Z |
| format | Article |
| id | doaj.art-b307ef46469042afa7addf5f215851a4 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T00:27:01Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-b307ef46469042afa7addf5f215851a42022-12-22T03:10:35ZengBMCBMC Cancer1471-24072017-06-0117111310.1186/s12885-017-3442-yTargeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosisXinfang Yu0Wei Li1Zhenkun Xia2Li Xie3Xiaolong Ma4Qi Liang5Lijun Liu6Jian Wang7Xinmin Zhou8Yifeng Yang9Haidan Liu10Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityDepartment of Thoracic Surgery, The Second Xiangya Hospital of Central South UniversityDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South UniversityDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityClinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South UniversityClinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South UniversityDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South UniversityClinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South UniversityClinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12885-017-3442-yEsophageal squamous cell carcinomaChemosensitizationMCL-1CisplatinApopotosis |
| spellingShingle | Xinfang Yu Wei Li Zhenkun Xia Li Xie Xiaolong Ma Qi Liang Lijun Liu Jian Wang Xinmin Zhou Yifeng Yang Haidan Liu Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis BMC Cancer Esophageal squamous cell carcinoma Chemosensitization MCL-1 Cisplatin Apopotosis |
| title | Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis |
| title_full | Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis |
| title_fullStr | Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis |
| title_full_unstemmed | Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis |
| title_short | Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis |
| title_sort | targeting mcl 1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin induced apoptosis |
| topic | Esophageal squamous cell carcinoma Chemosensitization MCL-1 Cisplatin Apopotosis |
| url | http://link.springer.com/article/10.1186/s12885-017-3442-y |
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