Gemcitabine (Gemzar, 2,2-difluorodeoxycytidine, or dFdC) is an analog of cytosine arabinoside with anti-tumor activity in a few human cancers (lung, ovary, pancreatic and breast cancers). However, the mechanism of apoptosis by this compound in carcinoma has not been fully elucidated. In the present study, we investigated that gemcitabine alone and combination with cisplatin or 5-FU are cancer toxicity using lung cancer cell line A549 by MTT, FACS analysis, and Western blot assay. Also, to confirm enhanced antitumor activity in vivo using an xenograft tumor model. The MTT assay showed higher cytotoxic effect in combination with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine alone. FACS analysis showed that gemcitabine-cisplatin combination increased hypodiploid DNA to 70.84 %. The induction of apoptosis showed more increase in combination with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine alone. The Western results showed higher expression of p53 and p21WAF/CIP1 protein in combination treatment with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine treatment alone. But, Bcl-2 protein expression decreased. In vivo experiments showed that more decreased tumor size and more increased survival rate on combination with gemcitabine- cisplatin or gemcitabine-5-FU combination than gemcitabine alone. In conclusion, this study suggests that gemcitabine combined with cisplatin or 5-FU are the synergistic effect of anticancer therapy on lung cancer.

I. INTRODUCTION
 II. MATERIALS and METHODS
  1. Cell culture and animal
  2. Cell viability analysis
  3. Cell cycle analysis
  4. DNA staining
  5. Western blot analysis
  6. Tumor xenograft efficacy studies
 III. RESULTS
  1. Cell growth inhibition
  2. Cell cycle analysis
  3. DNA staining
  4. Western blot analysis
  5. Tumor xenograft efficacy studies
 IV. DISCUSSION
 V. REFERENCES

• 박정희(Department of Oral Pathology, School of Dentistry, Pusan National University) | Jung Hee Park
• 안원근(Department of Oral Pathology, School of Dentistry, Pusan National University) | Won Gun An
• 박혜련(Department of Oral Pathology, School of Dentistry, Pusan National University) | Hae Ryoun Park correspondence