Low-dose zoledronic acid reduces spinal cord metastasis in pulmonary adenocarcinoma with neuroendocrine differentiation.
Zoledronic acid (ZOL), a nitrogen-containing compound, is effective in the treatment of skeletal disorders, but its long-term use in high doses gives rise to complications such as osteonecrosis. We aimed to investigate the effect of low-dose ZOL on the expression of the neural cell adhesion molecule (NCAM), which may be correlated with tumor growth and spinal cord metastasis in lung adenocarcinoma with neuroendocrine differentiation. First, we used the small hairpin RNA technique to directly knock down NCAM expression in cells of a murine lung adenocarcinoma line, line 1 cells, and found that the tumor cells generated showed lower invasive capacity, slower tumor growth, and lesser tendency for spinal cord metastasis than control cells. Further, ZOL decreased NCAM expression and invasiveness in line 1 tumor cells in vitro. Line 1/lacZ cells, a stable clone tagged with the lacZ gene, were introduced into mice, followed by ZOL treatment (1 μg/kg/weekly). Low-dose ZOL significantly reduced spinal cord metastasis probably through reduced NCAM expression in vivo. These findings indicated that NCAM is involved in tumor growth and spinal cord metastasis of lung adenocarcinoma with neuroendocrine differentiation. Treatment with low-dose ZOL can reduce NCAM expression that may contribute toward reduced spinal cord metastasis, suggesting that NCAM is an alternative therapeutic target and that the low-dose ZOL treatment protocol is a reasonable approach for its treatment.
Department of Internal Medicine, Division of Hemato-oncology, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Keelung, Taiwan.
Ying-Ying
YY
Li
John W-C
JW
Chang
Ling-Ling
LL
Hsieh
Shu-Mei
SM
Chen
Kun-Yun
KY
Yeh
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D019006:Neural Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D013120:Spinal Cord Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D014162:Transfection; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D019006:Neural Cell Adhesion Molecules; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D000077211:Zoledronic Acid