hSSTR2 expression and octreotide treatment reverses multidrug resistance of BxPC-3 human pancreatic cancer cells.
Pancreatic cancer is generally refractory to most chemotherapeutic agents. We investigated whether hSSTR2 expression and octreotide treatment reverse multidrug resistance of human pancreatic cancer cells. We used pancreatic cancer cells that were transfected by using a lentivirus expression system, which allowed stable expression of the hSSTR2 gene in the pancreatic cancer cells. BxPC-3 cells were transfected with hSSTR2 through a lentivirus vector pWP XL-MOD-SSTR2 in order to enable the expression of hSSTR2. The transfected cells were treated with different concentrations of octreotide and with the chemotherapeutic agents cisplatin, epirubicin, fluorouracil and gemcitabine. The changes in IC50 following treatment with chemotherapeutic agents were determined, and the expression of different MDR indicating marker genes, multidrug resistance gene-1 (MDR1), multidrug resistance-associated protein 2 (MRP2), and lung resistance-related protein (LRP), were evaluated. Octreotide treatment of the transfected cells significantly decreased the IC50 of chemotherapeutic agents in a dose-dependent manner. hSSTR2 gene transfection decreased MDR1, MRP2 and LRP expression by 57, 47 and 56%, respectively (P<0.01), and octreotide treatment (1.6 microg/ml) for 48 h, decreased it further by 88, 73 and 87<, respectively (P<0.01). These data suggested that the down-regulation of MDR genes is responsible for the improvement in the chemotherapeutic sensitivity of hSSTR2-expressing pancreatic cancer cells, when these cells are subjected to octreotide treatment.
Sui
Chenguang
C
Department of Oncology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, PR China.
Ma
Qingyong
Q
Nan
Kejun
K
Xiao
Juxiang
J
Suo
Aili
A
Sha
Huanchen
H
Zhao
Lei
L
D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D016086:Lentivirus / Q000235:genetics; D015282:Octreotide / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D017931:DNA Primers; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2; D015282:Octreotide