It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death.Tanshinone IIA(Tan IIA),an active ingredient of a commonly used traditional Chinese herb Salvia miltior...It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death.Tanshinone IIA(Tan IIA),an active ingredient of a commonly used traditional Chinese herb Salvia miltiorrhiza,provides a new direction to develop a new strategy for the treatment.It has been found that Tan IIA could inhibit lung cancer in vitro and in vivo by inducing autophagic apoptosis.Tan IIA increased apoptotic cells and the expression of cleaved caspase 3 and cleaved caspase 9,decreased B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax)ratio in human non-small cell lung cancer(NSCLC)cell lines,which was promoted by an autophagy activator Rapamycin,and weaken by autophagy inhibitor 3-methyladenine(3-MA).In addition,Tan IIA induced more autophagosomes,up-regulated light chain 3b(LC-3B)I and LC-3B II conversion and less sequestosome 1(SQSTM1/p62)expression,which cannot be weakened by the caspase 3 antagonist.Moreover,overexpression of LC-3B gene(LC3B)and downregulation of autophagic gene 5(ATG5)further confirmed that Tan IIA induced autophagic apoptosis in NSCLC cell lines.Beclin-1 gene(BECN1)overexpression and silence attenuated the effects of Tan IIA,suggesting autophagic apoptosis that Tan IIA induced was dependent on Beclin-1.Overall,our study demonstrated a new treatment mechanism of Tan IIA and suggested that Tan IIA is a potential new anti-cancer therapeutic option.展开更多
基金The study was supported by grants from the National Natural Science Foundation of China(81903943 and 82074219)the Natural Science Foundation of Guangdong Province(2017A030310502)+1 种基金The study was also supported by the Key Projects of Educational Commission of Guangdong Province(2018KZDXM020)the Science and Technology Planning Project of Guangzhou(202002030009).
文摘It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death.Tanshinone IIA(Tan IIA),an active ingredient of a commonly used traditional Chinese herb Salvia miltiorrhiza,provides a new direction to develop a new strategy for the treatment.It has been found that Tan IIA could inhibit lung cancer in vitro and in vivo by inducing autophagic apoptosis.Tan IIA increased apoptotic cells and the expression of cleaved caspase 3 and cleaved caspase 9,decreased B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax)ratio in human non-small cell lung cancer(NSCLC)cell lines,which was promoted by an autophagy activator Rapamycin,and weaken by autophagy inhibitor 3-methyladenine(3-MA).In addition,Tan IIA induced more autophagosomes,up-regulated light chain 3b(LC-3B)I and LC-3B II conversion and less sequestosome 1(SQSTM1/p62)expression,which cannot be weakened by the caspase 3 antagonist.Moreover,overexpression of LC-3B gene(LC3B)and downregulation of autophagic gene 5(ATG5)further confirmed that Tan IIA induced autophagic apoptosis in NSCLC cell lines.Beclin-1 gene(BECN1)overexpression and silence attenuated the effects of Tan IIA,suggesting autophagic apoptosis that Tan IIA induced was dependent on Beclin-1.Overall,our study demonstrated a new treatment mechanism of Tan IIA and suggested that Tan IIA is a potential new anti-cancer therapeutic option.