Quan, Yu Hua; Kim, Byungji; Park, Ji-Ho; Choi, Yeonho; Choi, Young Ho; Kim, Hyun Koo
Experimental lung research
2014Dec ; 40 ( 10 ) :475-84.
PMID : 25299431
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Quan, Yu Hua -
Kim, Byungji -
Park, Ji-Ho -
Choi, Yeonho -
Choi, Young Ho -
Kim, Hyun Koo -
ABSTRACT
In spite of severe side effects, chemotherapy is widely used as a major anticancer treatment in non-small cell lung cancer (NSCLC). In order to enhance the therapeutic properties and reduce side effects, enormous efforts have been devoted to direct anticancer agents specifically to tumor tissues by the use of nanoparticles, or cancer cell marker attached drugs. However, cell-specific chemotherapy is still in its infancy and is not applicable to all types of cancers due to the complexity of the cancer occurrence and progress. In this study, we demonstrate that hyaluronan (HA)-conjugated cisplatin has highly selective and sensitive anticancer effects in NSCLC cells that overexpress the trans-membrane receptor, CD44, as HA is a specific ligand for CD44. In proliferation experiments, HA-conjugated cisplatin showed dramatic cell viability decreases (from 100% to 42.31%) in H1299 cells, which overexpress CD44, whereas no such change was observed in A549 and HFL1, which have little to no expression of CD44. More importantly, conjugation with HA decreased the dosage concentration of cisplatin by 50-fold for both cytotoxic and anti-metastatic effects. In addition, HA-cisplatin conjugate treatment selectively decreased migration (from 100% to 7.8%) and invasiveness (from 100% to 21.4%, respectively) of H1299. Based on our experimental results, we strongly believe that HA-cisplatin conjugate is a potential anticancer chemo-agent, which target CD44 overexpression in NSCLC, with minimal side effects and high therapeutic properties.
keyword
CD44; hyaluronan-cisplatin conjugate; lung cancer
MESH
Adenocarcinoma/metabolism/pathology, Antibodies, Monoclonal/immunology/pharmacology, Antigens, CD44/immunology/*metabolism, Antineoplastic Agents/*pharmacology, Apoptosis/*drug effects, Carcinoma, Non-Small-Cell Lung/metabolism/*pathology, Cell Line, Cell Line, Tumor, Cell Movement/drug effects, Cell Proliferation/drug effects, Cell Survival/drug effects, Cisplatin/*pharmacology, Humans, Hyaluronic Acid/*pharmacology, Lung/drug effects/metabolism/pathology, Lung Neoplasms/metabolism/*pathology, Neoplasm Invasiveness/pathology, Up-Regulation/*physiology
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