Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

Xu, Linlin; Wang, Xin; Zou, Shengquan

doi:10.3748/wjg.14.2578

Cited by 14 publications

(19 citation statements)

References 32 publications

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“…(24,25) In this study using human gallbladders and cultures of gallbladder epithelial cells and the gallbladder carcinoma cell line, we assessed the expression pattern of EZH2 and class I HDACs (HDAC 1 and 2). We considered the possible mechanism by which carcinoma cells are sensitive to SAHA and the possible efficacy of this new anticancer agent in therapeutic treatment in gallbladder carcinoma.…”

Section: Ink4amentioning

confidence: 99%

Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma

et al. 2010

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Polycomb group protein EZH2, frequently overexpressed in malignant tumors, is the catalytic subunit of polycomb repressive complex 2 (PRC2). PRC2 interacts with HDACs in transcriptional silencing and relates to tumor suppressor loss. We examined the expression of HDAC isoforms (HDAC 1 and 2) and EZH2, and evaluated the possible use of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and EZH2 repressor for gallbladder carcinoma. We used 48 surgically resected gallbladders and cultures of human gallbladder epithelial cells (HGECs), gallbladder carcinoma (TGBC2TKB), and cholangiocarcinoma (HuCCT-1 and TFK-1) cell lines for examination. Immunohistochemically, EZH2 was overexpressed in gallbladder carcinoma, especially poorly differentiated carcinoma, but not in normal epithelium. In contrast, HDAC1/2 were expressed in both carcinoma and normal epithelium in vivo. This pattern was verified in cultured cells; EZH2 was highly expressed only in TGBC2TKB, whereas HDAC1/2 were expressed in HGECs and TGBC2TKB. Interestingly, SAHA treatment caused significant cell number decline in three carcinoma cells, and this effect was synergized with EZH2 siRNA treatment; however, HGECs were resistant to SAHA. In TGBC2TKB cells, the expression of EZH2 and HDAC1/2 were decreased by SAHA treatment, and p16 INK4a, E-cadherin, and p21 were simultaneously activated; however, no such findings were obtained in HGECs, suggesting that the effect of SAHA depends on the EZH2-mediated tumor suppressor loss. In conclusion, this study suggests a possible mechanism by which carcinoma cells but not normal cells are sensitive to SAHA and indicates the efficacy of this new anticancer agent in combination with EZH2 repression in gallbladder carcinoma. (Cancer Sci 2010; 101: 355-362) G allbladder carcinoma is an aggressive and depressing disease, particularly affecting older people and women. (1)(2)(3) It is usually difficult to detect gallbladder carcinoma in the early stage, because characteristic signs or symptoms are lacking and high risk factors have not been established in a majority of patients. Although complete surgical resection is the only curative therapy, invasion to surrounding organs or metastases is usually found in a majority of gallbladder carcinoma patients at the time of diagnosis. The current chemotherapy for patients with advanced gallbladder carcinoma is limited, and the development and exploration of new anticancer agents is necessary. (4,5) Polycomb group proteins are epigenetic chromatin modifiers involved in cancer development.(6,7) PcG proteins exist in at least two separate protein complexes, polycomb repressive complex 2 (PRC2) and PRC1. The PRC2 complex involves embryonic ectoderm development and EZH2. (8,9) EZH2 is a transcriptional repressor involved in controlling cell growth and proliferation and an abnormal expression of EZH2 may be involved in the tumorigenesis process and provides proliferative advantages to eukaryotic cells through interaction with the pathways of key elements that control cell growth arres...

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Section: Ink4amentioning

confidence: 99%

Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma

et al. 2010

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“…Однако в последние несколько десятилетий отмечается тен-денция к расширению возрастного диапазона [24,27], уже не нонсенс выявление холелитиаза в детском возрасте с частотой около 5% [12,21,30,39,40].…”

Section: факторы риска особенности клинического теченияunclassified

“…Резкое ограничение основных продуктов питания, их несбалансированность, а также голодание спо-собствуют камнеобразованию, так как эти факторы приводят к нарушению энтерогепатической цирку-ляции ЖК [14,21]. При длительном прерывании эн-терогепатической циркуляции, что наблюдается при голодании, оказывается недостаточно ЖК для обра-зования такого количества мицелл, которое необхо-димо для удержания холестерина в растворенном состоянии, вследствие чего желчь становится лито-генной [8,18,40]. После восстановления нормально-го питания БС исчезает практически у всех больных примерно через 4 недели [1,10,22].…”

Section: факторы риска особенности клинического теченияunclassified

“…В последние годы значительно увеличилось число операций по поводу ЖКБ, в связи с чем холецистэк-томия занимает уже второе место после аппендэкто-мии [2,25,40]. В мире выполняется ежегодно более 500 тыс.…”

Section: профилактикаunclassified

“…На нашей кафедре доказана эффективность сочетанного при-менения УДХК и полифепана [4] и УДХК и мине-ральной воды «Увинская» [5,6] при лечении БС. От-дельные сообщения имеются об уменьшении лито-генных свойств желчи на ранней стадии ЖКБ при применении хофитола и симвастатина [40].…”

Section: профилактикаunclassified

See 2 more Smart Citations

Gallstone Disease: Epidemiology, Risk Factors, Clinical Features, Prevention

Вахрушев¹,

Хохлачева²

2016

Arhivʺ vnutr. med.

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Next‐generation sequencing survey of biliary tract cancer reveals the association between tumor somatic variants and chemotherapy resistance

Ahn

Javle

Ahn

et al. 2016

Cancer

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Background BTC are uncommon and associated with a dismal prognosis. Gemcitabine and platinum-combinations (GP) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for GP response in BTC, we evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance. Methods Pretreatment FFPE samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression free survival (PFS) and overall survival (OS). Results Considering genes with an incidence >10%, no individual gene was independently predictive of GP response. In patients with unresectable BTC who received GP as first-line therapy, the joint status of CDKN2A, TP53 and ARID1A were associated with PFS (P=0.0004) and OS (P=<0.0001). Patients with mutations in CDKN2A and TP53 were identified as a poor prognostic cohort with a median PFS and OS of 2.63 and 5.22 months. Patients with mutant ARID1A regardless of single mutational status of TP53 or CDKN2A had similar outcomes. A patient who exhibited mutations in all three genes had a median PFS of 20.37 months and OS not reached. Conclusions In the largest exploratory analysis of this nature in BTC, the presence of three prevalent, mutually exclusive mutations represents distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker to GP response. Prospective studies validate these findings are needed, including the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC.

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Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

Cited by 14 publications

References 32 publications

Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma

Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma

Gallstone Disease: Epidemiology, Risk Factors, Clinical Features, Prevention

Next‐generation sequencing survey of biliary tract cancer reveals the association between tumor somatic variants and chemotherapy resistance

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