J Cancer 2020; 11(23):6790-6801. doi:10.7150/jca.47694

Research Paper

Effect of TTLL6 expression on CDDP sensitivity of EC109/CDDP cells in hypoxia/acidosis microenvironment

Yang Qiu1, Chao Wu1,2, Jingyao Li1, Meng Tang1, Shixin Zhang1, Tao Jing3, Yi Liao1✉, Haidong Wang1✉

1. Department of thoracic surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
2. State Key Laboratory of Silkworm Genome Biology, The Institute of Sericulture and Systems Biology, Southwest University, Chongqing, China.
3. Department of Cardiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

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Citation:
Qiu Y, Wu C, Li J, Tang M, Zhang S, Jing T, Liao Y, Wang H. Effect of TTLL6 expression on CDDP sensitivity of EC109/CDDP cells in hypoxia/acidosis microenvironment. J Cancer 2020; 11(23):6790-6801. doi:10.7150/jca.47694. Available from http://www.jcancer.org/v11p6790.htm

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Abstract

Multidrug resistance is a major obstacle to the effective treatment of esophageal carcinoma. It occurs more readily in hypoxia and acidosis microenvironment. TTLL6 is one of Tubulin tyrosine ligase-like family members. In this study, the effect of TTLL6 on the regulation of cisplatin (CDDP) sensitivity was evaluated in CDDP-resistant esophageal carcinoma (EC) cells both in vitro and in vivo. In hypoxia/acidosis condition, overexpression of TTLL6 in EC109/CDDP cells significantly lowered the IC50 of CDDP and increased the CDDP-induced apoptosis; while knockdown of TTLL6 expression in EC109/CDDP cells exhibited the opposite effects. Further study showed that, mechanistically, TTLL6 was inversely correlated with ERBB2 and TOPOIIA, and positively correlated with apoptosis-associated factor Caspase 9. Furthermore, animal model confirmed that TTLL6 negatively regulated the growth of xenograft tumor after chemotherapy. Alternated expression of TTLL6 also regulated the expression of ERBB2, TOPOIIA and Caspase 9 in EC109/CDDP cells in vivo. In conclusion, our results suggest that TTLL6 could reverse the drug resistant of EC109/CDDP cells, it might provide a potential treatment strategy for the clinical reversing the chemotherapy resistance.

Keywords: Chemotherapy, Drug resistance, EC109/CDDP, Hypoxia/Acidosis, TTLL6