title: Emodin reverses gemcitabine resistance in pancreatic cancer cells via             the mitochondrial apoptosis pathway in vitro.
abstract: Gemcitabine resistance is a common problem of pancreatic cancer chemotherapy, and how to reverse it plays an important role in the treatment of pancreatic cancer. This study investigated the effect of emodin on the gemcitabine-resistant pancreatic cancer cell line SW1990/Gem, and explored the potential mechanism of its action. SW1990/Gem was obtained by culture of the pancreatic cancer cell line SW1990 in vitro by intermittently increasing the concentration of gemcitabine in the culture medium for 10 months, observing the morphology using inverted microscopy. SW1990/Gem cells were pretreated with emodin (10 µM) for different periods followed by treatment with gemcitabine (20 µM) for 48 h; cell proliferation was tested by MTT assay. SW1990/Gem cells were treated by emodin with different concentrations for 48 h, cell apoptosis was detected by flow cytometry (FCM). The expression of gene and protein, such as MDR-1 (P-gp), NF-κB, Bcl-2, Bax, cytochrome-C (cytosol), caspase-9 and -3 were measured by RT-PCR and Western blotting. The function of P-gp in SW1990/Gem cells was checked by FCM. The results showed that the SW1990/Gem cells changed greatly in morphology and the resistance index was 48.63. Emodin promoted cell apoptosis of the gemcitabine-resistant cell line SW1990/Gem in a dose-dependent manner. Emodin enhanced the SW1990/Gem cell sensitivity to gemcitabine in a time-dependent manner. Emodin monotherapy or combination with gemcitabine both decreased the gene and protein expression levels of MDR-1 (P-gp), NF-κB and Bcl-2 and inhibited the function of P-gp, but increased the expression levels of Bax, cytochrome-C (cytosol), caspase-9 and -3, and promoted cell apoptosis. This demonstrated that emodin had a reversing effect on the gemcitabine-resistant cell line SW1990/Gem, possibly via decreasing the function of P-gp and activating the mitochondrial apoptosis pathway in vitro.
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical College, No 109, West Xue-yuan Road, Wenzhou 325027, PR China.
authors.forename: Dian-Lei
authors.initials: DL
authors.lastname: Liu
authors.forename: Heqi
authors.initials: H
authors.lastname: Bu
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Hong-Chun
authors.initials: HC
authors.lastname: Guo
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Wang
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Tong
authors.forename: Zhong-Lin
authors.initials: ZL
authors.lastname: Ni
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Liu
authors.forename: Sheng-Zhang
authors.initials: SZ
authors.lastname: Lin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004642:Emodin / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D000093542:Gemcitabine
chemical_list: D047428:Protein Kinase Inhibitors; D003841:Deoxycytidine; D004642:Emodin; D000093542:Gemcitabine