[Role of inhibition of transcription factor forkhead box M1 expression by RNA interference in the proliferation and invasiveness of non-small cell lung cancer cells].
OBJECTIVE
To investigate the change of proliferation and invasiveness of non-small cell lung cancer (NSCLC) cell lines SPC-A-1, A549 and LTEP-a-2 with forkhead box M1 (FoxM1) expression deficiency.


METHODS
A siRNA targeting FoxM1 was designed to deplete the FoxM1 expression of these cell lines and an unrelated siRNA used as control. Real-time RT-PCR and Western blotting were used to examine the FoxM1 expression in mRNA and protein level respectively. Colony assay, wound healing assay and transwell chamber assay were employed to evaluate the colony formation ability and invasiveness of FoxM1 deficient cells.


RESULTS
The designed siRNA could efficiently deplete FoxM1 expression by 83.9%, 83.6% and 88.6% in SPC-A-1, A549 and LTEP-a-2 cell lines respectively. Real-time RT-PCR and Western blot test showed that the FoxM1 protein was also depleted. The colony formation numbers (136.0 +/- 15.5, 87.0 +/- 2.6 and 121.7 +/- 9.4 respectively) and invasion cell numbers (19.2 +/- 2.5, 4.2 +/- 0.8 and 6.2 +/- 1.8 respectively) of FoxM1 deficient SPC-A-1, A549 and LTEP-a-2 cell lines were significantly fewer than those of the unrelated-siRNA transfected group (colony formation numbers were 222.3 +/- 20.5, 164.7 +/- 14.1 and 260.7 +/- 13.5 respectively, and invasive cell numbers were 81.4 +/- 6.2, 39.2 +/- 4.6 and 35.6 +/- 3.0 respectively, all P < 0.01). The cell migration rate of siFoxM1 deficient SPC-A-1 (52.6% +/- 7.8%) was significantly lower than that of the unrelated-siRNA transfected group (85.3% +/- 18.6%, P < 0.01).


CONCLUSIONS
The proliferation and invasiveness of several NSCLC cell lines were significantly inhibited after the FoxM1 gene expression was depleted. It suggests that inhibiting the FoxM1 expression might be a promising way for lung cancer therapy.
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Lei
L
Zhou
Ping-hai
PH
Zhang
Xin
X
Xu
Nuo
N
Xu
Lei
L
Gao
Chun-xue
CX
Bai
Xin
X
Zhang
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D034741:RNA, Small Interfering; D014162:Transfection
C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering