Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance

被引：55

作者：

Alam, Manzar ^{[1
]}

Kashyap, Tanushree ^{[1
]}

Mishra, Prajna ^{[2
]}

Panda, Aditya K. ^{[1
]}

Nagini, Siddavaram ^{[3
]}

Mishra, Rajakishore ^{[1
]}

机构：

[1] Cent Univ Jharkhand, Ctr Life Sci, Sch Nat Sci, Ratu Lohardaga Rd, Ranchi 835205, Jharkhand, India

[2] Cent Univ Jharkhand, Sch Nat Sci, Ctr Appl Chem, Ranchi, Jharkhand, India

[3] Annamalai Univ, Fac Sci, Dept Biochem & Biotechnol, Annamalainagar, Tamil Nadu, India

来源：

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK | 2019年 / 41卷 / 01期

关键词：

Akt; Bax; Bcl-2; chemoradiation resistance; drug resistance; GSK3; alpha; beta; oral cancer; oral squamous cell carcinoma; OSCC; p53; SINGLE-NUCLEOTIDE POLYMORPHISMS; TUMOR-SUPPRESSOR P53; MUTATIONAL INACTIVATION; CISPLATIN SENSITIVITY; PROTEIN EXPRESSION; DOWN-REGULATION; BREAST-CANCER; BCL-2; GENE; APOPTOSIS;

D O I：

10.1002/hed.25471

中图分类号：

R76 [耳鼻咽喉科学];

学科分类号：

100213 [耳鼻咽喉科学];

摘要：

Background Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive. Methods A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients were used. The status of Bax was analyzed at DNA/mRNA/protein levels and the results were correlated with p53 and Akt expression in tissue samples/cisplatin-resistant oral tongue SCC (SCC9/SCC4-CisR) cell line. Results Frequent progressive decrease of Bax expression with infrequent promoter methylation, polymorphisms G(-248)A, and mutations was observed in OSCC progression/resistance. Furthermore, by targeting Akt pathway, induction of Bax-dependent cell death was observed and this was further enhanced with nimbolide treatment in SCC9/SCC4-CisR cells. Conclusion Hence, the Bax gene alteration and its deregulation through p53/Akt pathway are important for OSCC progression and drug resistance. Akt Inhibitor VIII and nimbolide synergistically induce Bax, and it is therefore beneficial for chemosensitizing cisplatin-resistant human OSCC.

引用

页码：185 / 197

页数：13

共 56 条

[1]

Role of BAX mutations in mismatch repair-deficient colorectal carcinogenesis [J].