Zhi Guang Fu1, Yan Wang2, Shuang Wang3, Dan Shao3, Li Tian4, Yun Xia Li5, Jian Li Jiang6, Zhi Nan Chen6, Ning Wen7. 1. Department of Stomatology, Chinese PLA General Hospital, Beijing 100850, China; Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China. 2. Department of Internal Neurology, 309 Hospital of PLA, Beijing 100091, China. 3. Department of Stomatology, Huangdao District Central Hospital, Qingdao, 266000, Shandong, China. 4. Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China. 5. Outpatient Department, Special Police College of the Chinese Armed Police Force, Beijing 100621, China. 6. Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China. 7. Department of Stomatology, Chinese PLA General Hospital, Beijing 100850, China.
Abstract
OBJECTIVE: Cancer is a serious threat to human health. Despite extensive research on cancer treatment, there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound (AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored. METHODS: Wst-1 assays were used to confirm the effect of novel compounds on proliferation. Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism. RESULTS: There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway. CONCLUSION: Our results have clarified the tumor specificity of CD147 and its drug target characteristics. The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.
OBJECTIVE:Cancer is a serious threat to human health. Despite extensive research on cancer treatment, there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound (AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored. METHODS: Wst-1 assays were used to confirm the effect of novel compounds on proliferation. Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism. RESULTS: There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway. CONCLUSION: Our results have clarified the tumor specificity of CD147 and its drug target characteristics. The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.