Inhibition of cyclin D1 by shRNA is associated with enhanced sensitivity to conventional therapies for head and neck squamous cell carcinoma.
BACKGROUND
Overexpression of cyclin D1 is associated with resistance to chemotherapy and radiotherapy in several types of cancer including head and neck squamous cell carcinoma (HNSCC).


METHODS
Cyclin D1 was silenced in an HNSCC cell line and its effect tested in sensitizing the cells to cisplatin, in vitro as well as in vivo. The HNSCC cell line NT8e, which is a chemoresistant, cyclin D1 over-expressing cell line, was used in the study. RNAi (shRNA) against cyclin D1 was designed and cloned in a vector.


RESULTS
Stable silencing of cyclin D1 resulted in delayed cell cycle progression and significantly sensitized the cells to cisplatin. Effective cell kill was achieved at a much lower therapeutic dose in vivo.


CONCLUSIONS
Suboptimal concentrations of cisplatin could be used in vivo to eradicate xenograft tumors indicating the promise of combining vector-based cyclin D1 silencing with chemotherapy to achieve maximum tumor regression.
Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
Vishal
V
Kothari
Rita
R
Mulherkar
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D003114:Colony-Forming Units Assay; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D034741:RNA, Small Interfering; D019938:Cyclin D1; D002945:Cisplatin