Anticancer Effect Of Pingyangmycin, Hydroxylcamptothecin Or Their Combination Against Experimental Carcinoma Of Tongue And Their Effect On Radiosensitization

The incidence of carcinoma of tongue is about 0.5-0.6/105 in male and 0.4-0.5/105 in female, and it takes precedence in incidence of all kinds of tumors in oral cavity. Most of the carcinomas of the tongue can transfer to lymph nodes, and the proportion can reach 60%-80%. The five-year survival rate of the suffers is about 60% according to the P.R. China's data. Generally, synthetic therapies are adopted to treat patients because the single surgical treatment can not prevent the recurrence and metastasis of carcinoma of tongue. Chemotherapy and radiotherapy are the significant treatment of oncotherapy. The curative effect of pingyangmycin (PYM) for squamous cell carcinoma is acceptable, but it can not prevent recurrence and metastasis to distant tissue in some patients. The serious side effect such as pulmonary interstitial fibrosis would be take place if patients were overdosed the PYM. Hydroxycampothecin (HCPT) is usually used to treat hepatom, gastroenteric tumor or bladder carcinoma. Its capability of antitumor is powerful. It has a little side effect for its lower toxicity and it is valid to many kinds of tumors. It is very few that the study about the combination chemotherapy of PYM and HCPT. It was only reported byChenpeng at 2001 that PYM in combination with HCPT had moresignificant anticancer effects for Tca8113 in vitro.Objective: To study the therapeutic effect of the combinationchemotherapy of PYM and HCPT to oral squamous cell carcinoma andthe sensitization of concomitant radiotherapy .Methods:1. Human Tca8113 cell line xenograft in nude mice were established for studies. Antitumor activity of PYM, HCPT or their combination on Tca8113 xenograft of nude mice were determined. Tumor inhibitory rates are calculated and nude mice survival rates are recorded.2. To determine apoptotic cells percentage of xenograft in nude mice in every group by TUNEL kit. Analyse apoptotic cell percentage of xenograft treated differentlly.3. To detect the effect of radiosensitization of PYM, HCPT or their combination by counting living cells of human Tca8113 cell line according trypanblau. To caculate the DT(population doubling time) of different treatment groups by cell counting.4. To compare the effect of radiosensitization of PYM, HCPT or their combination by caculating antitumor inhibitory rates of different treatment groups and the nude mice survival time.Result:1. PYM and HCPT showed similar antitumor effects and their inhibitory rates were 45±18.2% and 41±16.1% respectively. PYM in combination with HCPT had more significant anticancer effects for Tca8113 in vivo than by HCPT or PYM alone. Antitumor rate of the combination group was 74±14.7%, which had a statistical significance compared with the single groups(p<0.01). Its antitumor activity wasmore significant. One of the nude mice of control was dead when the treatment lasted 28 days. At last, the survival rates of the single treatment groups was 3/5 and it was 4/5 in combination gpoup but the nude mice of control were dead wholly.2. Apoptotic cell percentage of xenograft detected by TUNEL kit were 5±2% (control), 18±5% (PYM), 21±3% (HCPT) and 57 ± 5% (combination) respectively. The combination group's apoptotic percentage was higher compared with single groups, which had a statistical significance. The single groups showed similar tumor cell apoptotic percentage.3. Each therapic group's cell survival rates decreased by counting living cells of human Tca8113 cell line according trypanblau. All the treatment groups except the radiotherapy had a statistical significance compared with the control group. The cell survival rate of each concomitant radiotherapy group was decreased compared with the corresponding chemotherapy group. They are statistical different compared with the corresponding chemotherapy groups. There was no statistical difference between the groups which were radiated after adding chemotherapeutics 24h and the corresponding chemotherapy groups (p>0.05) . The DT in Tca8113 of treatment groups were 30.1h (contral), 36.4h (PYM), 42.6h (HCPT), 49.6h (PYM+HCPT) respectively, and the groups' DT of PYM, HCPT or their combination associated with radiotherapy at the same time were 46.5h, 55.9h and 60.2h respectively. DT of the last three groups acceptted PYM, HCPT or their combination in 24h radiated 2 Gy X-ray were 38.9h, 43.6h and 48.7h. It was 31.6h when the Tca8113 had been radiated singly. The concomitant radiotherapy groups had more significant anticancer effects for Tca8113 in vitro than the chemotherapic groups correspondingly.4. The antitumor inhibitionrates were observed after human Tca8113 cell line xenograft in nude mice radiated associated with PYM, HCPT or their combination. They were 25 + 6.2% (radiotherapy), 50 ±16.5% (PYM), 46 + 19.2% (HCPT), 67+18.6% (P+H), 68±13.5% (PYM combined radiotherapy), 60+12.3% (HCPT combined radiotherapy) and 80+14.5% (PYM+HCPT combined radiotherapy) respectively. Tumor inhibitory rates of each concomitant radiotherapy group were increased compared with the corresponding chemotherapy group. The concomitant radiotherapy groups had more significant anticancer effects for Tca8113 in vivo than the corresponding chemotherapy groups. There was statistical significance between them(p<0.01). Conclusion:1. PYM, HCPT or their combination showed antitumor effects significantly when they were used for human Tca8113 cell line xenograft in nude mice. PYM combined HCPT had better antitumor effect than they were used singly.2. TUNEL kit proved that apoptosis counting of PYM combined with HCPT is statistical different from that of PYM or HCPT. PYM combined with HCPT can induce more apoptosis of xenograft.3. There was radiosensitization effect wether PYM, HCPT or their combination were used for Tca8113 cell line in vitro. The concomitant radiotherapy has better inhibiting activity to Tca8113 cell compared with radiotherapy or chemotherapy.4. Concomitant chemoradiotherapy of PYM, HCPT or their combination had better antitumor effect than radiotherapy or chemotherapy in vivo.In conclusion, PYM, HCPT or their combination have significant antitumor activity to tongue carcinoma especially when their...