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phase regulation.
In our study, we found that SKLB826 which had remarkable efficacy to inhibit human liver cancer in
remarkably induced G2/M arrest in HepG2 and Bel7402 cell vitro and in vivo. In vitro, SKLB826 inhibited cell cycle progres-
lines, so we chose to investigate the change of G2/M related sion via inhibiting the activities of the cyclinA2 and cyclinB1–
proteins and we found SKLB826 treatment signicantly CDK1 complex and further induced apoptosis through the
decreased the expression of cdc25c and CDK1. Furthermore, mitochondria-mediated intrinsic pathway. In vivo, SKLB826
some studies have been reported recently that cyclinA2 can displayed a strong antitumor activity in the human liver cancer
combine with CDK1 and the cyclinA2–CDK1 complex can acti- xenogra without causing any signicant toxicities. In addition,
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vate the cyclinB1–CDK1 complex in proliferating somatic cells.
the synthesis of SKLB826 is easy to achieve. Hence, the
To further investigate the mechanism of the G2/M phase arrest compelling evidence indicated that SKLB826 may be a potential
induced by SKLB826, the expression of cyclinA2 was measured. candidate for the development of new anti-HCC drug.
In our study, we found that the levels of cyclinA2 down regu-
lated, which further validated that SKLB826 treatment caused
G2/M arrest.
References
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ꢂ1
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SKLB826 to improve the pharmacokinetic properties.
In conclusion, through constantly optimizing the structure
of benzothiazole derivatives, we got the compound SKLB826
1410–1426.
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41350 | RSC Adv., 2015, 5, 41341–41351
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