| Targeting therpy is one kind of antitumor methods, that is through attacking or changing some kinds of molecules to spectively inhibit the growth of tumor cells. At present, EGFR is an inspiring target. Iressa and Tarceva have been being used in clinic and reduced some patients' pain and increased the survival rate. However, there are still many problerns to be resolved. Because data suggests that Iressa and Tarceva could play their roles on one part of their own given patients.How can we predict the given patients according to molecular signalling and the characteristic analysising? How can we improve their effects because physicians are not satisfied with their intensity? How can we reduce Iressa and Tarceva's severe side effect of ILD (interstitial lung disease ) in clinic? How can we synthesize a better medicine ? What mechanism is in the medicine because Iressa and Tarceva could be effective on patients whose EGFR level is low?BP3323 is synthesized chemically by a domestic pharmaceutical company Beta with their own patent in China and in America, which is similar to Iressa and Tarceva in chemical structure. In elementary invitro and in vivo studies, BP3323 was proved to be more effective and lesspoisonous than Iressa and Tarceva. In this study, nine human carcinoma cell lines from epidermis were selected and their EGFR levels were determined with Western-blot. In four colorectal carcinoma cell lines, the EGFR level of SW480 is the highest, and CaCO2 and RKO are next to SW480, while the EGFR level of SW620 is not detectable in this study. In addition, the EGFR of oral carcinoma cell line KB> uterus carcinoma cell line Hel^ gastric carcinoma cell line AGS and breast caininoma cell line MCF-7 are all overexpressed, while the EGFR level of hepatitic carcinoma cell line HepG2 is low. We selected two human colorectal carcinoma cell lines of SW480 and SW620 that express high level of EGFR and very low level of EGFR respectively and cytotoxity> apoptosis and FCM would be determined under the condition of BP3323.The results are showed as follows: EGFR is overexpressed in SW480, KB, HeLa, AGS, CaCO2 and MCF-7 and is expressed relatively low in SW620, RKO and HepG2. The IC50 of SW480 and SW620 treated with BP3323 (concentration from 0-250 uM) for 48 hours are 75uM and 80uM respectively. Near the IC50, 75uM was selected in this study. Apoptosis was not distinctly observed by morphologic and AnnexinV in SW480 and SW620 treated with 75uM BP3323 for 48 hours. The apoptosis rate was 3.29%(0.59% in control) and necrosis rate was 0.29% (0.10% in control)in SW480;the apoptosis rate was 2.02%(1.68% in control) and necorsis rate was 0.32%(0.29% in control);while FCM showed the cell cycle of SW480 was arrested in G0/G1 phase(66.3%, 60.3% in control) and G2/M phase(17.6%,13.7% in control) and the cell cycle of SW620 was arrested in G2/M phase(22.0%, 12.5% in control).We concluded that:BP3323 which targets EGFR-TK could inhibit the growth of SW480 whose EGFR level is high and SW620 whose EGFR level is low, and these effects could be carried out through different cell cycle arrest under spective concentration. |
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