ALA-PDT suppressing the cell growth and reducing the lipogenesis in human SZ95 sebocytes by mTOR signaling pathway in vitro.
BACKGROUND
5-Aminolevulinic acid mediated -photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, the therapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate the effects and mechanisms of ALA-PDT on the cell growth and lipogenesis of human SZ95 sebocytes.


METHODS
Human SZ95 sebocytes were treated with different concentration of ALA-PDT.CCK-8 assay was used to detect cell proliferation activity. Fluorescence microscope and flow cytometry were used to observe the secretion of lipids in SZ95 cells after Nile red staining. Western blotting was used to detect and analyze the protein expression level of P-p70 S6K/p70 S6K, P-4E-BP1/4E-BP1, SREBP-1, PPARγ, P-mTOR/mTOR, and P-Raptor/Raptor. Mean while, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences on the ALA-PDT treatment of SZ95 cells.


RESULTS
ALA-PDT suppressed the cell growth and reduced the secretion of lipids in a dose-dependent manner in SZ95 cells. ALA-PDT reduced the protein levels of P-p70 S6K (T389), SREBP-1, PPARγ, P-mTOR and P-Raptor. IGF-1 had counter effects on ALA-PDT, and rapamycin enhanced the effects of ALA-PDT in SZ95 cells in suppressing the cell growth and reducing the secretion of lipids.


CONCLUSIONS
ALA-PDT suppressed the cell growth in SZ95 cells by mTOR-p70 S6K(T389) signaling and reduced the lipogenesis in SZ95 cells by mTOR-SREBP-1/PPARγ signaling. Sebaceous glands atrophy and reduction of sebum secretion after ALA-PDT may be caused by the suppression of lipogenesis and cell growth in sebocytes.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Jiang
J
Tuo
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Qianqian
Q
Wang
Departments of Dermatology, Venereology, Allergology and Immunology Dessau Medical Center Auenweg 38, 06847 Dessau, Germany.
Christos C
CC
Zouboulis
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Ye
Y
Liu
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Ying
Y
Ma
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Li
L
Ma
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Jiayi
J
Ying
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Chengfeng
C
Zhang
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China. Electronic address: flora_xiang@vip.163.com.
Leihong
L
Xiang
D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D012627:Sebaceous Glands / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
5-Aminolevulinic acid; Lipogenesis; Photodynamic therapy; Sebocytes; mTOR