Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

Tepsiri, Nisana; Chaturat, Liengchai; Sripa, Banchob; Namwat, Wises; Wongkham, Sopit; Bhudhisawasdi, Vajarabhongsa; Tassaneeyakul, Wichittra

doi:10.3748/wjg.v11.i18.2748

Cited by 84 publications

(80 citation statements)

References 35 publications

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“…In a previous study, MRP1 and MRP3 have been reported to be highly expressed in the five human CCA cell lines, while MRP2 was only moderately expressed and MDR1 expression was detected only in one cell line. A strong correlation was also found between the level of MRP3 expression and the IC 50 values of the anticancer drugs etopocide, doxorubicin, and pirarubicin (Tepsiri et al, 2005). Consistent with this finding, a strong association between MRP3 mRNA level and response to doxorubicin has been reported in lung cancer (Young et al, 1999).…”

Section: Discussionmentioning

confidence: 56%

Cytotoxicity, Toxicity, and Anticancer Activity of Zingiber Officinale Roscoe Against Cholangiocarcinoma

Plengsuriyakarn¹,

Viyanant²,

Eursitthichai³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/ DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median IC 50 (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and 27.86 μg/ml, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.

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Section: Discussionmentioning

confidence: 56%

Cytotoxicity, Toxicity, and Anticancer Activity of Zingiber Officinale Roscoe Against Cholangiocarcinoma

Plengsuriyakarn¹,

Viyanant²,

Eursitthichai³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Downregulation and/or impaired activity of enzymes involved in gemcitabine and 5-fluorouracil activation, such as thymidine phosphoryl ase, uridine phosphorylase 1 and uridine monophosphate synthetase, reduce the sensitivity of CCA to these drugs 287,288 . The phase II enzyme glutathione S-transferase P is highly expressed in CCA, which might have an important role in inactivating drugs by conjugation with glutathione 289,290 . Changes in molecular targets could also affect the response to chemotherapy (MOC-3).…”

Section: Mechanisms Of Chemoresistancementioning

confidence: 99%

“…Thymidylate synthase has a key role in the sensitivity of CCA to 5-fluorouracil 291 . Although some controversy exists 278,288,290 , simvastatin has been shown to boost the 5-fluorouracil effect in CCA cells by suppressing thymidyl ate synthase expression 292 . Expression of ERs in CCA 93 justifies its sensitivity to tamoxifen 293 and KB9520, which activates apoptosis in experimental CCA 94 .…”

Section: Mechanisms Of Chemoresistancementioning

confidence: 99%

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,107

1,139

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“…Likewise, overexpression of MRP1 (multidrug resistance-related protein-1), another protein of the ABC family of transporters, is associated with chemoresistance in primary liver tumors and consequent poor prognosis [48,49]. Consistent with this, a 2005 study of Tepsiri and colleagues that evaluated in five human CC cell lines, the expression of several genes involved in multidrug resistance, found that all of them express MRP1 [50].…”

Section: Molecular and Genetic Alterationsmentioning

confidence: 83%

Cholangiocarcinoma: from molecular biology to treatment

et al. 2015

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Cholangiocarcinoma is a rare tumor originating in the bile ducts, which, according to their anatomical location, is classified as intrahepatic, extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in recent decades. With respect to tumor biology, several genetic alterations correlated with resistance to chemotherapy and radiotherapy have been identified. Here, we highlight changes in KRAS and TP53 genes that are normally associated with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family appear to be involved in the resistance that the cholangiocarcinoma presents toward conventional therapies. With regard to diagnosis, tumor markers most commonly used are CEA and CA 19-9, and although its use isolated appears controversial, their combined value has been increasingly advocated. In imaging terms, various methods are needed, such as abdominal ultrasound, computed tomography and cholangiopancreatography. Regarding therapy, surgical modalities are the only ones that offer chance of cure; however, due to late diagnosis, most patients cannot take advantage of them. Thus, the majority of patients are directed to other therapeutic modalities like chemotherapy, which, in this context, assumes a purely palliative role. Thus, it becomes urgent to investigate new therapeutic options for this highly aggressive type of tumor.

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Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

Cited by 84 publications

References 35 publications

Cytotoxicity, Toxicity, and Anticancer Activity of Zingiber Officinale Roscoe Against Cholangiocarcinoma

Cytotoxicity, Toxicity, and Anticancer Activity of Zingiber Officinale Roscoe Against Cholangiocarcinoma

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma: from molecular biology to treatment

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