In vitro and in vivo studies on the inhibitory effects of myocardial cell culture medium on growth of a human lung adenocarcinoma cell line, A549

Abstract

Background: Although the heart is one of the body's vital organs, with an abundant blood supply, metastasis to the heart is considered rare. In a previous study, we found that the myocardial microenvironment might contain a low molecular weight natural tumour suppressor. The present study was designed to investigate the inhibitory effect of cardiac myocyte-conditioned medium (cmcm) on the growth of A549 human lung adenocarcinoma cells in vitro and in vivo.

Methods: An mtt assay was used to detect the inhibition ratio with respect to A549 proliferation. Human lung adenocarcinoma cells (A549 cell strain) were transplanted subcutaneously into nude mice to produce tumours. The xenograft tumour growth in mice was observed after selected drug administration.

Results: After treatment with cmcm and cisplatin (Cis), A549 cell viability significantly declined (p < 0.001). The cell viability in the cmcm and Cis groups were 53.42% ± 3.45% and 58.45% ± 6.39% respectively. Growth of implanted tumour cells in vivo was significantly inhibited in the cmcm group, the group treated with recombinant human adenovirus-p53, and the Cis-treated group compared with a control group. The inhibition rates were 41.44% in the cmcm group, 41.34% in the p53 group, and 64.50% in the Cis group. Lung metastasis capacity was significantly reduced in the presence of cmcm (p < 0.05). Lung metastasis inhibition rates in mice were 56.52% in the cmcm group, 47.83% in the p53 group, and 82.61% in the Cis group. With cmcm, the lives of A549-tumour-bearing mice could be significantly prolonged without any effect on weight loss.

Conclusions: Use of cmcm has the effect of reducing A549 cell viability, tumour volume, and lung metastasis rate, while prolonging survival duration without severe toxicity.

Keywords: Cardiac myocyte–conditioned medium; lung adenocarcinoma; metastasis; nude mice; tumour inhibition.

FIGURE 1

Growth curves for lung cancer tumour xenografts implanted in nude mice. NS = control group (normal saline); CMCM = treated with cardiac myocyte–conditioned medium; P53 = treated with recombinant human adenovirus–p53; DDP = treated with cisplatin.

FIGURE 2

Antitumour efficacy of cardiac myocyte–conditioned medium (CMCM) in vivo. (A,B) An inhibitory effect of CMCM on the weight of lung cancer tumour xenografts implanted in nude mice is observed. NS = control group (normal saline); DDP = treated with cisplatin; P53 = treated with recombinant human adenovirus–p53; CMCM = treated with CMCM. * p < 0.001 compared with the control group.

FIGURE 3

Effects of cardiac myocyte–conditioned medium (CMCM) on survival rate and side effects in tumour-bearing mice. (A) Treatment with CMCM was more effective than treatment with cisplatin (DDP) or recombinant human adenovirus–p53 (P53) for increasing the survival of tumour-bearing mice. (B) Treatment with CMCM had no effect on weight loss in tumour-bearing mice. NS = control group (normal saline).

FIGURE 4

Inhibition of tumour metastasis (A549 lung carcinoma cells) in mice. (A) Control group [NS (normal saline)], (B) group treated with cardiac myocyte–conditioned medium (CMCM), (C) group treated with recombinant human adenovirus–p53 (P53), (D) group treated with cisplatin (DDP), and (E) overall occurrence of metastases in each group. * p < 0.05 compared with control group.