Multidrug resistance and tumor-initiating capacity of oral cancer stem cells.
OBJECTIVE
Recent studies in several tumors showed that presence of cancer stem like side population (SP) cells are responsible for chemotherapeutic drugs resistance and tumor relapse. In our present study, we have analyzed the role of SP cells in oral squamous cell carcinoma cell (OSCC) line OSCC-77.


METHODS
The oral cancer cell line OSCC-77 was analyzed for the presence of SP cells by FACS using Hoechst 33342 dye exclusion method. Further the FACS-sorted SP and non-SP cells were subjected to drug resistance and sphere formation assays.


RESULTS
We identified that the presence of SP cells in OSCC-77 cell line was 3.4%, which was reduced to 0.6% in the presence of verapamil, an inhibitor of ABC transporter. Furthermore, we showed that these SP cells were highly drug-resistant, had increased survival and were highly potent for self-renewal. Also, the clone formation efficiency of SP cells was significantly higher compared to non-SP cells (p<0.01).


CONCLUSIONS
Our data suggest that cancer stem-like SP cells of OSCC-77 cell line contribute to multidrug resistance and are highly involved in tumor relapse. However, further characterization of SP cells at gene expression level and their signaling pathways might provide new insights into the development of novel anticancer drugs.
School of Dentistry, Shandong University, Shandong 250012, China;
Hong-Guo
HG
Shang
Hong-Ling
HL
Yu
Xiao-Ni
XN
Ma
Xin
X
Xu
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058985:Side-Population Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D014700:Verapamil