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

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 IC 50 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.

Identification of hypoxia‐related gene signatures based on multi‐omics analysis in lung adenocarcinoma

“…In the liver metastatic tissue derived from patients of colorectal cancer, SCGB2A1 was identified as a novel hypoxia‐inducible gene and prognostic marker associated with chemoresistance and radioresistance 75 . In hypoxia condition, overexpression of TTLL6 significantly lowered the IC50 of cisplatin (CDDP) and increased the CDDP‐induced apoptosis in EC109/ CDDP cells 76 . Moreover, hypoxia downregulates LPP3 (cg11959316) during cancer cell invasion 77 .…”

“… 75 In hypoxia condition, overexpression of TTLL6 significantly lowered the IC50 of cisplatin (CDDP) and increased the CDDP‐induced apoptosis in EC109/ CDDP cells. 76 Moreover, hypoxia downregulates LPP3 (cg11959316) during cancer cell invasion. 77 According to our literature search results, the remaining genes have not yet been found to be directly related to hypoxia.…”

An in vitro chronic damage model impairs inflammatory and regenerative responses in human colonoid monolayers

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