Antitumor effects of an imidazoquinoline in renal cell carcinoma.
OBJECTIVE
To evaluate the effects of imidazoquinolines in renal cell carcinoma (RCC).


METHODS
In vitro experiments were carried out using mouse (RENCA) and human (CAKI-1, CAKI-2, and A-498) RCC cell lines. Toll-like receptor-7 (TLR7) expression was assessed by Western blot. We determined the ability of imidazoquinolines to induce apoptosis and inhibit cell viability in vitro. For in vivo experiments, RENCA cells were injected into the tail vein of syngeneic mice. One week after injection, mice were given oral imidazoquinoline or placebo for 14 days. Mice were then sacrificed, and lungs were inspected for tumor nodules. Immunohistochemical staining was used to assess apoptosis in vivo.


RESULTS
Toll-like receptor-7 was expressed in all cell lines tested, with RENCA cells showing the highest level of expression. Imidazoquinolines inhibited in vitro cell viability of RENCA, CAKI-2, and A-498 cell lines in a time-dependent manner. Viability of CAKI-1 was not inhibited significantly. Apoptosis induction was pronounced in RENCA cells treated with imidazoquinoline. Compared with placebo, oral imidazoquinoline significantly reduced the number of pulmonary metastasis and increased cell death in vivo.


CONCLUSIONS
Imidazoquinolines inhibit cell viability and cause deoxyribonucleic acid fragmentation leading to apoptosis in RCC cell lines, potentially working through the TLR7 expressed by RCC cell lines. Preliminary data from a mouse model of metastatic RCC also suggest antitumor effects and induction of apoptosis in vivo.
Schwartz
Michael J
MJ
Department of Urology, New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, New York 10021, USA.
Liu
Huixian
H
Hwang
David H
DH
Kawamoto
Hideki
H
Scherr
Douglas S
DS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011804:Quinolines / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D051199:Toll-Like Receptor 7 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D007093:Imidazoles; D011804:Quinolines; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7