Persistence of side population cells with high drug efflux capacity in pancreatic cancer.
OBJECTIVE
To investigate the persistence of side population (SP) cells in pancreatic cancer and their role and mechanism in the drug resistance.


METHODS
The presentation of side population cells in pancreatic cancer cell line PANC-1 and its proportion change when cultured with Gemcitabine, was detected by Hoechst 33342 staining and FACS analysis. The expression of ABCB1 and ABCG2 was detected by real-time PCR in either SP cells or non-SP cells.


RESULTS
SP cells do exist in PANC-1, with a median of 3.3% and a range of 2.1-8.7%. After cultured with Gemcitabine for 3 d, the proportion of SP cells increased significantly (3.8% +/- 1.9%, 10.7% +/- 3.7%, t = 4.616, P = 0.001 < 0.05). ABCB1 and ABCG2 expressed at higher concentrations in SP as compared with non-SP cells (ABCB1: 1.15 +/- 0.72, 5.82 +/- 1.16, t = 10.839, P = 0.000 < 0.05; ABCG2: 1.16 +/- 0.75, 5.48 +/- 0.94, t = 11.305, P = 0.000 < 0.05), which may contribute to the efflux of fluorescent staining and drug resistance.


CONCLUSIONS
SP cells with inherently high resistance to chemotherapeutic agents do exist in pancreatic cancers, which may be candidate cancer stem cells contributing to the relapse of the tumor.
Zhou
Jing
J
Institute of Pancreatic Surgery, Union Hospital, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei Province, China.
Wang
Chun-You
CY
Liu
Tao
T
Wu
Bin
B
Zhou
Feng
F
Xiong
Jiong-Xin
JX
Wu
He-Shui
HS
Tao
Jing
J
Zhao
Gang
G
Yang
Ming
M
Gou
Shan-Miao
SM
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D000093542:Gemcitabine
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C073119:TAP1 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine