In Vivo Experiment On The Inhibition Of Growth Of Human SKOV₃ Ovarian Neoplasms With TNP-470

The format ion of a blood supply (angiogenesis) is critical to thegrowth of solid tumrs, including ovarian neoplasms. Safe and effectivangiogenesis inhibitors are needed to determine whether control ofangiogenesis would be therapeutic. TNP-470 has been used in thetreatment of many kinds of tumors of â… - â…¡ termclinical trials. Howev r,ln the field of ovarian neoplasms, TNP-470 was seldcom studied. Thantitumor effect of an angiogenesis inhibitor TNP-470 [AGM-1470, 0-(chloroacetylcarbamoyl) ], one of the most effective antiangiogenicdrugs by now. was investigated in nude mice implanted s. c. with humanovarian cancer (SKOV₃). After implantation, The nude mice were dividedinto 7 groups at random. saline solution was given s. c. to the controlgroup, the second group received a vehicle composed of 1% ethanol plus5%gum arabic in saline ("vehicle" for short). TNP-470 in different doses(25mg/kg, 50 mg/kg, 100 mg/kg) were given s. c. in the following thregroups, CTX (100 mg/kg) was used i. p. to treat the sixth group at the samtime. and the last one were treated with the combination of TNP-470(50mg/kg) and CTX (100mg/kg). CTX was injected i. p. once a week fromday 8 after implantation to day 28, TNP-470 was injected s. c. thretimes a week in the same period of time, and all the mice were sacrificedon day 28. We observed the inhibition of tumor growth through weighingand reasuring the tumor. valuing the expression of PCNA quantitatingmicrovessels, detecting the apoptos is and necrosis in tissues of everygroup by Evision and Tunel's techniques.There has no difference in the volume of implanted tumors beforedrug inj ction. Compar d with th vehicl or control group, TNP-470alon with Iow or medium dos s had no significant ff ct on the tumorgroWth in vivo (p>0. 05), with the inhibit rate at 2. 42X and 19. 8Xseparate I y; TNP--470 with h igh doses had a more s ign if icant effectcmpar i ng wi th the veh ic l e group (p<0. 05), its i nh ib it rate was 37. 6X;The cboi nat ion one showed a much h igher inh ib it effect than thseparate groups with the rate at 70. 5X. The more TNP--470 was given,the rore effects couId be observed. These ind icate that TNP--470 hada strong dose--dependent i nh ib itory act iv ity aga inst in v ivo ovar ianneop l asms, more over, CTX and TNP--470 had an add it ive effect on tumori nh i b it i on.Express ions of PCNA in TNP--470 group with h igh--dose i s a I itt l eIower than those in vehicle or controf group, and PCNA express ionsi n the CTX or i n the conb i nat ion one i s obv ious l y l ower, even ccoparedwith the h ighest dosed TNP--470 group; ^nd more, PCN^ express ion inCTX group doesn' t be affected by even med iumdosed TNP--470. More over.it couId be founded that the number of apoptosic ceI I s at randco inthe TNP--470 treated groups were far more than that i n the contro l groupwhich had no necrot ic t issues, whereas the nunIber of tumr necros isis on the contrary. Un I ike CTX, maybe TNP--470 inh ib ited the groWthof tumor ce l l s by ischemi a instead of d i rect l y prevent ing synthes isand mytosi s of DNA of turor cel l s.TNP--470 can obv ious I y decrease dens ity of m i croang i on. No matterwhether TNP--470 cou Id suppress the tumor ce I I s d i rect l y, it must bebenef ic ia l in prevent i ng the groWth of in s ite tumor and metastas i s,i nc I ud i ng ovar i an neop l asms.